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1. Integrated multimodal cell atlas of Alzheimer’s disease

Author

Gabitto, Mariano I., Travaglini, Kyle J., Rachleff, Victoria M., Kaplan, Eitan S., Long, Brian, Ariza, Jeanelle, Ding, Yi, Mahoney, Joseph T., Dee, Nick, Goldy, Jeff, Melief, Erica J., Agrawal, Anamika, Kana, Omar, Zhen, Xingjian, Barlow, Samuel T., Brouner, Krissy, Campos, Jazmin, Campos, John, Carr, Ambrose J., Casper, Tamara, Chakrabarty, Rushil, Clark, Michael, Cool, Jonah, Dalley, Rachel, Darvas, Martin, Ding, Song-Lin, Dolbeare, Tim, Egdorf, Tom, Esposito, Luke, Ferrer, Rebecca, Fleckenstein, Lynn E., Gala, Rohan, Gary, Amanda, Gelfand, Emily, Gloe, Jessica, Guilford, Nathan, Guzman, Junitta, Hirschstein, Daniel, Ho, Windy, Hupp, Madison, Jarsky, Tim, Johansen, Nelson, Kalmbach, Brian E., Keene, Lisa M., Khawand, Sarah, Kilgore, Mitchell D., Kirkland, Amanda, Kunst, Michael, Lee, Brian R., Leytze, Mckaila, Mac Donald, Christine L., Malone, Jocelin, Maltzer, Zoe, Martin, Naomi, McCue, Rachel, McMillen, Delissa, Mena, Gonzalo, Meyerdierks, Emma, Meyers, Kelly P., Mollenkopf, Tyler, Montine, Mark, Nolan, Amber L., Nyhus, Julie K., Olsen, Paul A., Pacleb, Maiya, Pagan, Chelsea M., Peña, Nicholas, Pham, Trangthanh, Pom, Christina Alice, Postupna, Nadia, Rimorin, Christine, Ruiz, Augustin, Saldi, Giuseppe A., Schantz, Aimee M., Shapovalova, Nadiya V., Sorensen, Staci A., Staats, Brian, Sullivan, Matt, Sunkin, Susan M., Thompson, Carol, Tieu, Michael, Ting, Jonathan T., Torkelson, Amy, Tran, Tracy, Valera Cuevas, Nasmil J., Walling-Bell, Sarah, Wang, Ming-Qiang, Waters, Jack, Wilson, Angela M., Xiao, Ming, Haynor, David, Gatto, Nicole M., Jayadev, Suman, Mufti, Shoaib, Ng, Lydia, Mukherjee, Shubhabrata, Crane, Paul K., Latimer, Caitlin S., Levi, Boaz P., Smith, Kimberly A., Close, Jennie L., Miller, Jeremy A., Hodge, Rebecca D., Larson, Eric B., Grabowski, Thomas J., Hawrylycz, Michael, Keene, C. Dirk, and Lein, Ed S.

Published
2024
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2. Single-cell DNA methylation and 3D genome architecture in the human brain.

Author

Lucero, Jacinta, Osteen, Julia, Emerson, Nora, Rink, Jon, Lee, Jasper, Li, Yang, Siletti, Kimberly, Liem, Michelle, Claffey, Naomi, OConnor, Carolyn, Yanny, Anna, Nyhus, Julie, Dee, Nick, Casper, Tamara, Shapovalova, Nadiya, Hirschstein, Daniel, Ding, Song-Lin, Hodge, Rebecca, Levi, Boaz, Keene, C, Linnarsson, Sten, Lein, Ed, Ren, Bing, Behrens, M, Ecker, Joseph, Liu, Hanqing, Castanon, Rosa, Kenworthy, Mia, Altshul, Jordan, Valadon, Cynthia, Aldridge, Andrew, Nery, Joseph, Chen, Huaming, Xu, Jiaying, Tian, Wei, Zhou, Jingtian, Bartlett, Anna, Zeng, Qiurui, and Johnson, Nicholas

Abstract

Delineating the gene-regulatory programs underlying complex cell types is fundamental for understanding brain function in health and disease. Here, we comprehensively examined human brain cell epigenomes by probing DNA methylation and chromatin conformation at single-cell resolution in 517 thousand cells (399 thousand neurons and 118 thousand non-neurons) from 46 regions of three adult male brains. We identified 188 cell types and characterized their molecular signatures. Integrative analyses revealed concordant changes in DNA methylation, chromatin accessibility, chromatin organization, and gene expression across cell types, cortical areas, and basal ganglia structures. We further developed single-cell methylation barcodes that reliably predict brain cell types using the methylation status of select genomic sites. This multimodal epigenomic brain cell atlas provides new insights into the complexity of cell-type-specific gene regulation in adult human brains.

Published
2023

3. A guide to the BRAIN Initiative Cell Census Network data ecosystem

Author

Hawrylycz, Michael, Martone, Maryann E, Ascoli, Giorgio A, Bjaalie, Jan G, Dong, Hong-Wei, Ghosh, Satrajit S, Gillis, Jesse, Hertzano, Ronna, Haynor, David R, Hof, Patrick R, Kim, Yongsoo, Lein, Ed, Liu, Yufeng, Miller, Jeremy A, Mitra, Partha P, Mukamel, Eran, Ng, Lydia, Osumi-Sutherland, David, Peng, Hanchuan, Ray, Patrick L, Sanchez, Raymond, Regev, Aviv, Ropelewski, Alex, Scheuermann, Richard H, Tan, Shawn Zheng Kai, Thompson, Carol L, Tickle, Timothy, Tilgner, Hagen, Varghese, Merina, Wester, Brock, White, Owen, Zeng, Hongkui, Aevermann, Brian, Allemang, David, Ament, Seth, Athey, Thomas L, Baker, Cody, Baker, Katherine S, Baker, Pamela M, Bandrowski, Anita, Banerjee, Samik, Bishwakarma, Prajal, Carr, Ambrose, Chen, Min, Choudhury, Roni, Cool, Jonah, Creasy, Heather, D’Orazi, Florence, Degatano, Kylee, Dichter, Benjamin, Ding, Song-Lin, Dolbeare, Tim, Ecker, Joseph R, Fang, Rongxin, Fillion-Robin, Jean-Christophe, Fliss, Timothy P, Gee, James, Gillespie, Tom, Gouwens, Nathan, Zhang, Guo-Qiang, Halchenko, Yaroslav O, Harris, Nomi L, Herb, Brian R, Hintiryan, Houri, Hood, Gregory, Horvath, Sam, Huo, Bingxing, Jarecka, Dorota, Jiang, Shengdian, Khajouei, Farzaneh, Kiernan, Elizabeth A, Kir, Huseyin, Kruse, Lauren, Lee, Changkyu, Lelieveldt, Boudewijn, Li, Yang, Liu, Hanqing, Liu, Lijuan, Markuhar, Anup, Mathews, James, Mathews, Kaylee L, Mezias, Chris, Miller, Michael I, Mollenkopf, Tyler, Mufti, Shoaib, Mungall, Christopher J, Orvis, Joshua, Puchades, Maja A, Qu, Lei, Receveur, Joseph P, Ren, Bing, Sjoquist, Nathan, Staats, Brian, Tward, Daniel, van Velthoven, Cindy TJ, Wang, Quanxin, Xie, Fangming, Xu, Hua, Yao, Zizhen, and Yun, Zhixi

Subjects
Biological Sciences, Genetics, Neurosciences, Mental Health, Data Science, 1.1 Normal biological development and functioning, Neurological, Animals, Humans, Mice, Brain, Ecosystem, Neurons, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.

Published
2023

4. Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

Bakken, Trygve E, Jorstad, Nikolas L, Hu, Qiwen, Lake, Blue B, Tian, Wei, Kalmbach, Brian E, Crow, Megan, Hodge, Rebecca D, Krienen, Fenna M, Sorensen, Staci A, Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D, Aldridge, Andrew I, Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G, Crichton, Kirsten, Daigle, Tanya L, Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T, Herb, Brian R, Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S, Liu, Hanqing, Lucero, Jacinta D, Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A, Moussa, Marmar, Nery, Joseph R, Nicovich, Philip R, Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K, Owen, Scott, Palmer, Carter R, Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M, Rimorin, Christine, Rivkin, Angeline, Romanow, William J, Sedeño-Cortés, Adriana E, Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A, Behrens, M Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R, Höllt, Thomas, Horwitz, Gregory D, Keene, C Dirk, Kharchenko, Peter V, Ko, Andrew L, Lelieveldt, Boudewijn P, Luo, Chongyuan, Mukamel, Eran A, Pinto-Duarte, António, Preissl, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H, Smith, Kimberly, Spain, William J, White, Owen R, Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z, McCarroll, Steven A, and Ting, Jonathan T

Subjects
Human Genome, Neurosciences, Genetics, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Atlases as Topic, Callithrix, Epigenesis, Genetic, Epigenomics, Female, GABAergic Neurons, Gene Expression Profiling, Glutamates, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Middle Aged, Motor Cortex, Neurons, Organ Specificity, Phylogeny, Single-Cell Analysis, Species Specificity, Transcriptome, General Science & Technology
Abstract

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Published
2021

5. A multimodal cell census and atlas of the mammalian primary motor cortex

Author

Callaway, Edward M, Dong, Hong-Wei, Ecker, Joseph R, Hawrylycz, Michael J, Huang, Z Josh, Lein, Ed S, Ngai, John, Osten, Pavel, Ren, Bing, Tolias, Andreas Savas, White, Owen, Zeng, Hongkui, Zhuang, Xiaowei, Ascoli, Giorgio A, Behrens, M Margarita, Chun, Jerold, Feng, Guoping, Gee, James C, Ghosh, Satrajit S, Halchenko, Yaroslav O, Hertzano, Ronna, Lim, Byung Kook, Martone, Maryann E, Ng, Lydia, Pachter, Lior, Ropelewski, Alexander J, Tickle, Timothy L, Yang, X William, Zhang, Kun, Bakken, Trygve E, Berens, Philipp, Daigle, Tanya L, Harris, Julie A, Jorstad, Nikolas L, Kalmbach, Brian E, Kobak, Dmitry, Li, Yang Eric, Liu, Hanqing, Matho, Katherine S, Mukamel, Eran A, Naeemi, Maitham, Scala, Federico, Tan, Pengcheng, Ting, Jonathan T, Xie, Fangming, Zhang, Meng, Zhang, Zhuzhu, Zhou, Jingtian, Zingg, Brian, Armand, Ethan, Yao, Zizhen, Bertagnolli, Darren, Casper, Tamara, Crichton, Kirsten, Dee, Nick, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Dougherty, Elizabeth L, Fong, Olivia, Goldman, Melissa, Goldy, Jeff, Hodge, Rebecca D, Hu, Lijuan, Keene, C Dirk, Krienen, Fenna M, Kroll, Matthew, Lake, Blue B, Lathia, Kanan, Linnarsson, Sten, Liu, Christine S, Macosko, Evan Z, McCarroll, Steven A, McMillen, Delissa, Nadaf, Naeem M, Nguyen, Thuc Nghi, Palmer, Carter R, Pham, Thanh, Plongthongkum, Nongluk, Reed, Nora M, Regev, Aviv, Rimorin, Christine, Romanow, William J, Savoia, Steven, Siletti, Kimberly, Smith, Kimberly, Sulc, Josef, Tasic, Bosiljka, Tieu, Michael, Torkelson, Amy, Tung, Herman, van Velthoven, Cindy TJ, Vanderburg, Charles R, Yanny, Anna Marie, Fang, Rongxin, Hou, Xiaomeng, Lucero, Jacinta D, Osteen, Julia K, Pinto-Duarte, Antonio, and Poirion, Olivier

Subjects
Genetics, Neurosciences, Human Genome, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Atlases as Topic, Callithrix, Epigenomics, Female, Gene Expression Profiling, Glutamates, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Motor Cortex, Neurons, Organ Specificity, Phylogeny, Single-Cell Analysis, Species Specificity, Transcriptome, BRAIN Initiative Cell Census Network, General Science & Technology
Abstract

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

Published
2021

6. Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons

Author

Hodge, Rebecca D, Miller, Jeremy A, Novotny, Mark, Kalmbach, Brian E, Ting, Jonathan T, Bakken, Trygve E, Aevermann, Brian D, Barkan, Eliza R, Berkowitz-Cerasano, Madeline L, Cobbs, Charles, Diez-Fuertes, Francisco, Ding, Song-Lin, McCorrison, Jamison, Schork, Nicholas J, Shehata, Soraya I, Smith, Kimberly A, Sunkin, Susan M, Tran, Danny N, Venepally, Pratap, Yanny, Anna Marie, Steemers, Frank J, Phillips, John W, Bernard, Amy, Koch, Christof, Lasken, Roger S, Scheuermann, Richard H, and Lein, Ed S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Neurosciences, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Brain, Electrophysiology, Gene Expression Profiling, Humans, In Situ Hybridization, Fluorescence, Mice, Neurons, Pyramidal Cells, Telencephalon, Temporal Lobe, Transcriptome
Abstract

von Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identifies a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results suggest that VENs are a regionally distinctive type of ET neuron. Additionally, we describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.

Published
2020

7. Progress update from the hippocampal subfields group

Author

Olsen, Rosanna K, Carr, Valerie A, Daugherty, Ana M, La Joie, Renaud, Amaral, Robert SC, Amunts, Katrin, Augustinack, Jean C, Bakker, Arnold, Bender, Andrew R, Berron, David, Boccardi, Marina, Bocchetta, Martina, Burggren, Alison C, Chakravarty, M Mallar, Chételat, Gaël, de Flores, Robin, DeKraker, Jordan, Ding, Song‐Lin, Geerlings, Mirjam I, Huang, Yushan, Insausti, Ricardo, Johnson, Elliott G, Kanel, Prabesh, Kedo, Olga, Kennedy, Kristen M, Keresztes, Attila, Lee, Joshua K, Lindenberger, Ulman, Mueller, Susanne G, Mulligan, Elizabeth M, Ofen, Noa, Palombo, Daniela J, Pasquini, Lorenzo, Pluta, John, Raz, Naftali, Rodrigue, Karen M, Schlichting, Margaret L, Shing, Yee Lee, Stark, Craig EL, Steve, Trevor A, Suthana, Nanthia A, Wang, Lei, Werkle‐Bergner, Markus, Yushkevich, Paul A, Yu, Qijing, Wisse, Laura EM, and Group, Hippocampal Subfields

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Hippocampus, Volumetry, Human, Neuroimaging, Structural imaging, Neuroanatomy, Histology, Cytoarchitecture, ex vivo, Hippocampal Subfields Group, ex vivo, Genetics, Biological psychology
Abstract

IntroductionHeterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence.MethodsOur international working group, funded by the EU Joint Programme-Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption.ResultsThis progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures.DiscussionA harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide.

Published
2019

8. Conserved cell types with divergent features in human versus mouse cortex.

Author

Hodge, Rebecca D, Bakken, Trygve E, Miller, Jeremy A, Smith, Kimberly A, Barkan, Eliza R, Graybuck, Lucas T, Close, Jennie L, Long, Brian, Johansen, Nelson, Penn, Osnat, Yao, Zizhen, Eggermont, Jeroen, Höllt, Thomas, Levi, Boaz P, Shehata, Soraya I, Aevermann, Brian, Beller, Allison, Bertagnolli, Darren, Brouner, Krissy, Casper, Tamara, Cobbs, Charles, Dalley, Rachel, Dee, Nick, Ding, Song-Lin, Ellenbogen, Richard G, Fong, Olivia, Garren, Emma, Goldy, Jeff, Gwinn, Ryder P, Hirschstein, Daniel, Keene, C Dirk, Keshk, Mohamed, Ko, Andrew L, Lathia, Kanan, Mahfouz, Ahmed, Maltzer, Zoe, McGraw, Medea, Nguyen, Thuc Nghi, Nyhus, Julie, Ojemann, Jeffrey G, Oldre, Aaron, Parry, Sheana, Reynolds, Shannon, Rimorin, Christine, Shapovalova, Nadiya V, Somasundaram, Saroja, Szafer, Aaron, Thomsen, Elliot R, Tieu, Michael, Quon, Gerald, Scheuermann, Richard H, Yuste, Rafael, Sunkin, Susan M, Lelieveldt, Boudewijn, Feng, David, Ng, Lydia, Bernard, Amy, Hawrylycz, Michael, Phillips, John W, Tasic, Bosiljka, Zeng, Hongkui, Jones, Allan R, Koch, Christof, and Lein, Ed S

Subjects
Cerebral Cortex, Astrocytes, Neurons, Animals, Humans, Mice, Species Specificity, Neural Inhibition, Principal Component Analysis, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Biological Evolution, Single-Cell Analysis, Transcriptome, RNA-Seq, Genetics, Neurosciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Aetiology, Underpinning research, Neurological, General Science & Technology
Abstract

Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.

Published
2019

9. Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type

Author

Boldog, Eszter, Bakken, Trygve E, Hodge, Rebecca D, Novotny, Mark, Aevermann, Brian D, Baka, Judith, Bordé, Sándor, Close, Jennie L, Diez-Fuertes, Francisco, Ding, Song-Lin, Faragó, Nóra, Kocsis, Ágnes K, Kovács, Balázs, Maltzer, Zoe, McCorrison, Jamison M, Miller, Jeremy A, Molnár, Gábor, Oláh, Gáspár, Ozsvár, Attila, Rózsa, Márton, Shehata, Soraya I, Smith, Kimberly A, Sunkin, Susan M, Tran, Danny N, Venepally, Pratap, Wall, Abby, Puskás, László G, Barzó, Pál, Steemers, Frank J, Schork, Nicholas J, Scheuermann, Richard H, Lasken, Roger S, Lein, Ed S, and Tamás, Gábor

Subjects
Biomedical and Clinical Sciences, Neurosciences, Genetics, Brain Disorders, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Adult, Aged, Axons, Cerebral Cortex, Dendritic Spines, GABAergic Neurons, Gap Junctions, Gene Library, Humans, Male, Polymerase Chain Reaction, Presynaptic Terminals, Pyramidal Cells, RNA, Sequence Analysis, RNA, Transcriptome, Psychology, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

We describe convergent evidence from transcriptomics, morphology, and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single-nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a group of human interneurons with anatomical features never described in rodents, having large 'rosehip'-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1+CCK+, CNR1-SST-CALB2-PVALB-) matching a single transcriptomically defined cell type whose specific molecular marker signature is not seen in mouse cortex. Rosehip cells in layer 1 make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons, and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.

Published
2018

10. A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Author

Yao, Zizhen, van Velthoven, Cindy T.J., Nguyen, Thuc Nghi, Goldy, Jeff, Sedeno-Cortes, Adriana E., Baftizadeh, Fahimeh, Bertagnolli, Darren, Casper, Tamara, Chiang, Megan, Crichton, Kirsten, Ding, Song-Lin, Fong, Olivia, Garren, Emma, Glandon, Alexandra, Gouwens, Nathan W., Gray, James, Graybuck, Lucas T., Hawrylycz, Michael J., Hirschstein, Daniel, Kroll, Matthew, Lathia, Kanan, Lee, Changkyu, Levi, Boaz, McMillen, Delissa, Mok, Stephanie, Pham, Thanh, Ren, Qingzhong, Rimorin, Christine, Shapovalova, Nadiya, Sulc, Josef, Sunkin, Susan M., Tieu, Michael, Torkelson, Amy, Tung, Herman, Ward, Katelyn, Dee, Nick, Smith, Kimberly A., Tasic, Bosiljka, and Zeng, Hongkui

Published
2021
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11. Anatomical structures, cell types and biomarkers of the Human Reference Atlas

Author

Börner, Katy, Teichmann, Sarah A., Quardokus, Ellen M., Gee, James C., Browne, Kristen, Osumi-Sutherland, David, Herr, II, Bruce W., Bueckle, Andreas, Paul, Hrishikesh, Haniffa, Muzlifah, Jardine, Laura, Bernard, Amy, Ding, Song-Lin, Miller, Jeremy A., Lin, Shin, Halushka, Marc K., Boppana, Avinash, Longacre, Teri A., Hickey, John, Lin, Yiing, Valerius, M. Todd, He, Yongqun, Pryhuber, Gloria, Sun, Xin, Jorgensen, Marda, Radtke, Andrea J., Wasserfall, Clive, Ginty, Fiona, Ho, Jonhan, Sunshine, Joel, Beuschel, Rebecca T., Brusko, Maigan, Lee, Sujin, Malhotra, Rajeev, Jain, Sanjay, and Weber, Griffin

Published
2021
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12. Human neocortical expansion involves glutamatergic neuron diversification

Author

Berg, Jim, Sorensen, Staci A., Ting, Jonathan T., Miller, Jeremy A., Chartrand, Thomas, Buchin, Anatoly, Bakken, Trygve E., Budzillo, Agata, Dee, Nick, Ding, Song-Lin, Gouwens, Nathan W., Hodge, Rebecca D., Kalmbach, Brian, Lee, Changkyu, Lee, Brian R., Alfiler, Lauren, Baker, Katherine, Barkan, Eliza, Beller, Allison, Berry, Kyla, Bertagnolli, Darren, Bickley, Kris, Bomben, Jasmine, Braun, Thomas, Brouner, Krissy, Casper, Tamara, Chong, Peter, Crichton, Kirsten, Dalley, Rachel, de Frates, Rebecca, Desta, Tsega, Lee, Samuel Dingman, D’Orazi, Florence, Dotson, Nadezhda, Egdorf, Tom, Enstrom, Rachel, Farrell, Colin, Feng, David, Fong, Olivia, Furdan, Szabina, Galakhova, Anna A., Gamlin, Clare, Gary, Amanda, Glandon, Alexandra, Goldy, Jeff, Gorham, Melissa, Goriounova, Natalia A., Gratiy, Sergey, Graybuck, Lucas, Gu, Hong, Hadley, Kristen, Hansen, Nathan, Heistek, Tim S., Henry, Alex M., Heyer, Djai B., Hill, DiJon, Hill, Chris, Hupp, Madie, Jarsky, Tim, Kebede, Sara, Keene, Lisa, Kim, Lisa, Kim, Mean-Hwan, Kroll, Matthew, Latimer, Caitlin, Levi, Boaz P., Link, Katherine E., Mallory, Matthew, Mann, Rusty, Marshall, Desiree, Maxwell, Michelle, McGraw, Medea, McMillen, Delissa, Melief, Erica, Mertens, Eline J., Mezei, Leona, Mihut, Norbert, Mok, Stephanie, Molnar, Gabor, Mukora, Alice, Ng, Lindsay, Ngo, Kiet, Nicovich, Philip R., Nyhus, Julie, Olah, Gaspar, Oldre, Aaron, Omstead, Victoria, Ozsvar, Attila, Park, Daniel, Peng, Hanchuan, Pham, Trangthanh, Pom, Christina A., Potekhina, Lydia, Rajanbabu, Ramkumar, Ransford, Shea, Reid, David, Rimorin, Christine, Ruiz, Augustin, Sandman, David, Sulc, Josef, Sunkin, Susan M., Szafer, Aaron, Szemenyei, Viktor, Thomsen, Elliot R., Tieu, Michael, Torkelson, Amy, Trinh, Jessica, Tung, Herman, Wakeman, Wayne, Waleboer, Femke, Ward, Katelyn, Wilbers, René, Williams, Grace, Yao, Zizhen, Yoon, Jae-Geun, Anastassiou, Costas, Arkhipov, Anton, Barzo, Pal, Bernard, Amy, Cobbs, Charles, de Witt Hamer, Philip C., Ellenbogen, Richard G., Esposito, Luke, Ferreira, Manuel, Gwinn, Ryder P., Hawrylycz, Michael J., Hof, Patrick R., Idema, Sander, Jones, Allan R., Keene, C. Dirk, Ko, Andrew L., Murphy, Gabe J., Ng, Lydia, Ojemann, Jeffrey G., Patel, Anoop P., Phillips, John W., Silbergeld, Daniel L., Smith, Kimberly, Tasic, Bosiljka, Yuste, Rafael, Segev, Idan, de Kock, Christiaan P. J., Mansvelder, Huibert D., Tamas, Gabor, Zeng, Hongkui, Koch, Christof, and Lein, Ed S.

Published
2021
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14. The Allen Mouse Brain Common Coordinate Framework: A 3D Reference Atlas

Author

Wang, Quanxin, Ding, Song-Lin, Li, Yang, Royall, Josh, Feng, David, Lesnar, Phil, Graddis, Nile, Naeemi, Maitham, Facer, Benjamin, Ho, Anh, Dolbeare, Tim, Blanchard, Brandon, Dee, Nick, Wakeman, Wayne, Hirokawa, Karla E., Szafer, Aaron, Sunkin, Susan M., Oh, Seung Wook, Bernard, Amy, Phillips, John W., Hawrylycz, Michael, Koch, Christof, Zeng, Hongkui, Harris, Julie A., and Ng, Lydia

Published
2020
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17. A comprehensive transcriptional map of primate brain development.

Author

Bakken, Trygve E, Miller, Jeremy A, Ding, Song-Lin, Sunkin, Susan M, Smith, Kimberly A, Ng, Lydia, Szafer, Aaron, Dalley, Rachel A, Royall, Joshua J, Lemon, Tracy, Shapouri, Sheila, Aiona, Kaylynn, Arnold, James, Bennett, Jeffrey L, Bertagnolli, Darren, Bickley, Kristopher, Boe, Andrew, Brouner, Krissy, Butler, Stephanie, Byrnes, Emi, Caldejon, Shiella, Carey, Anita, Cate, Shelby, Chapin, Mike, Chen, Jefferey, Dee, Nick, Desta, Tsega, Dolbeare, Tim A, Dotson, Nadia, Ebbert, Amanda, Fulfs, Erich, Gee, Garrett, Gilbert, Terri L, Goldy, Jeff, Gourley, Lindsey, Gregor, Ben, Gu, Guangyu, Hall, Jon, Haradon, Zeb, Haynor, David R, Hejazinia, Nika, Hoerder-Suabedissen, Anna, Howard, Robert, Jochim, Jay, Kinnunen, Marty, Kriedberg, Ali, Kuan, Chihchau L, Lau, Christopher, Lee, Chang-Kyu, Lee, Felix, Luong, Lon, Mastan, Naveed, May, Ryan, Melchor, Jose, Mosqueda, Nerick, Mott, Erika, Ngo, Kiet, Nyhus, Julie, Oldre, Aaron, Olson, Eric, Parente, Jody, Parker, Patrick D, Parry, Sheana, Pendergraft, Julie, Potekhina, Lydia, Reding, Melissa, Riley, Zackery L, Roberts, Tyson, Rogers, Brandon, Roll, Kate, Rosen, David, Sandman, David, Sarreal, Melaine, Shapovalova, Nadiya, Shi, Shu, Sjoquist, Nathan, Sodt, Andy J, Townsend, Robbie, Velasquez, Lissette, Wagley, Udi, Wakeman, Wayne B, White, Cassandra, Bennett, Crissa, Wu, Jennifer, Young, Rob, Youngstrom, Brian L, Wohnoutka, Paul, Gibbs, Richard A, Rogers, Jeffrey, Hohmann, John G, Hawrylycz, Michael J, Hevner, Robert F, Molnár, Zoltán, Phillips, John W, Dang, Chinh, Jones, Allan R, Amaral, David G, Bernard, Amy, and Lein, Ed S

Subjects
Brain, Neocortex, Animals, Macaca mulatta, Humans, Microcephaly, Risk Factors, Schizophrenia, Cell Adhesion, Species Specificity, Transcription, Genetic, Conserved Sequence, Aging, Female, Male, Neurogenesis, Intellectual Disability, Transcriptome, Spatio-Temporal Analysis, Autism Spectrum Disorder, Neurodevelopmental Disorders, Transcription, Genetic, General Science & Technology
Abstract

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey (Macaca mulatta) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey.

Published
2016

18. Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: Towards a harmonized segmentation protocol

Author

Yushkevich, Paul A, Amaral, Robert SC, Augustinack, Jean C, Bender, Andrew R, Bernstein, Jeffrey D, Boccardi, Marina, Bocchetta, Martina, Burggren, Alison C, Carr, Valerie A, Chakravarty, M Mallar, Chételat, Gaël, Daugherty, Ana M, Davachi, Lila, Ding, Song-Lin, Ekstrom, Arne, Geerlings, Mirjam I, Hassan, Abdul, Huang, Yushan, Iglesias, J Eugenio, La Joie, Renaud, Kerchner, Geoffrey A, LaRocque, Karen F, Libby, Laura A, Malykhin, Nikolai, Mueller, Susanne G, Olsen, Rosanna K, Palombo, Daniela J, Parekh, Mansi B, Pluta, John B, Preston, Alison R, Pruessner, Jens C, Ranganath, Charan, Raz, Naftali, Schlichting, Margaret L, Schoemaker, Dorothee, Singh, Sachi, Stark, Craig EL, Suthana, Nanthia, Tompary, Alexa, Turowski, Marta M, Van Leemput, Koen, Wagner, Anthony D, Wang, Lei, Winterburn, Julie L, Wisse, Laura EM, Yassa, Michael A, Zeineh, Michael M, and Group, for the Hippocampal Subfields

Subjects
Biomedical and Clinical Sciences, Biomedical Imaging, Neurosciences, Adult, Clinical Protocols, Hippocampus, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Parahippocampal Gyrus, Medial temporal lobe, Hippocampal subfields, CA1, CA2, CA3, Dentate gyrus, Subiculum, Entorhinal cortex, Perirhinal cortex, Parahippocampal gyrus, Magnetic resonance imaging, Segmentation, Unified protocol, Hippocampal Subfields Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveAn increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol.MethodMRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement.ResultsThe differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail.ConclusionsThe combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.

Published
2015

19. Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

Author

Wuestefeld, Anika, primary, Baumeister, Hannah, additional, Adams, Jenna N., additional, de Flores, Robin, additional, Hodgetts, Carl J., additional, Mazloum‐Farzaghi, Negar, additional, Olsen, Rosanna K., additional, Puliyadi, Vyash, additional, Tran, Tammy T., additional, Bakker, Arnold, additional, Canada, Kelsey L., additional, Dalton, Marshall A., additional, Daugherty, Ana M., additional, La Joie, Renaud, additional, Wang, Lei, additional, Bedard, Madigan L., additional, Buendia, Esther, additional, Chung, Eunice, additional, Denning, Amanda, additional, del Mar Arroyo‐Jiménez, María, additional, Artacho‐Pérula, Emilio, additional, Irwin, David J., additional, Ittyerah, Ranjit, additional, Lee, Edward B., additional, Lim, Sydney, additional, del Pilar Marcos‐Rabal, María, additional, Iñiguez de Onzoño Martin, Maria Mercedes, additional, Lopez, Monica Munoz, additional, de la Rosa Prieto, Carlos, additional, Schuck, Theresa, additional, Trotman, Winifred, additional, Vela, Alicia, additional, Yushkevich, Paul, additional, Amunts, Katrin, additional, Augustinack, Jean C., additional, Ding, Song‐Lin, additional, Insausti, Ricardo, additional, Kedo, Olga, additional, Berron, David, additional, and Wisse, Laura E. M., additional

Published
2024
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20. Transcriptional landscape of the prenatal human brain.

Author

Miller, Jeremy A, Ding, Song-Lin, Sunkin, Susan M, Smith, Kimberly A, Ng, Lydia, Szafer, Aaron, Ebbert, Amanda, Riley, Zackery L, Royall, Joshua J, Aiona, Kaylynn, Arnold, James M, Bennet, Crissa, Bertagnolli, Darren, Brouner, Krissy, Butler, Stephanie, Caldejon, Shiella, Carey, Anita, Cuhaciyan, Christine, Dalley, Rachel A, Dee, Nick, Dolbeare, Tim A, Facer, Benjamin AC, Feng, David, Fliss, Tim P, Gee, Garrett, Goldy, Jeff, Gourley, Lindsey, Gregor, Benjamin W, Gu, Guangyu, Howard, Robert E, Jochim, Jayson M, Kuan, Chihchau L, Lau, Christopher, Lee, Chang-Kyu, Lee, Felix, Lemon, Tracy A, Lesnar, Phil, McMurray, Bergen, Mastan, Naveed, Mosqueda, Nerick, Naluai-Cecchini, Theresa, Ngo, Nhan-Kiet, Nyhus, Julie, Oldre, Aaron, Olson, Eric, Parente, Jody, Parker, Patrick D, Parry, Sheana E, Stevens, Allison, Pletikos, Mihovil, Reding, Melissa, Roll, Kate, Sandman, David, Sarreal, Melaine, Shapouri, Sheila, Shapovalova, Nadiya V, Shen, Elaine H, Sjoquist, Nathan, Slaughterbeck, Clifford R, Smith, Michael, Sodt, Andy J, Williams, Derric, Zöllei, Lilla, Fischl, Bruce, Gerstein, Mark B, Geschwind, Daniel H, Glass, Ian A, Hawrylycz, Michael J, Hevner, Robert F, Huang, Hao, Jones, Allan R, Knowles, James A, Levitt, Pat, Phillips, John W, Sestan, Nenad, Wohnoutka, Paul, Dang, Chinh, Bernard, Amy, Hohmann, John G, and Lein, Ed S

Subjects
Brain, Neocortex, Fetus, Animals, Humans, Mice, Anatomy, Artistic, Species Specificity, Gene Expression Regulation, Developmental, Conserved Sequence, Gene Regulatory Networks, Atlases as Topic, Transcriptome, Anatomy, Artistic, Gene Expression Regulation, Developmental, General Science & Technology
Abstract

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Published
2014

21. Comparison of histological delineation of the entorhinal, perirhinal, ectorhinal, and parahippocampal cortices by different neuroanatomy laboratories

Author

Baumeister, Hannah, primary, Wuestefeld, Anika, additional, Adams, Jenna N., additional, Bakker, Arnold, additional, Daugherty, Ana M., additional, de Flores, Robin, additional, Hodgetts, Carl J, additional, La Joie, Renaud, additional, Mazloum‐Farzaghi, Negar, additional, Olsen, Rosanna K, additional, Puliyadi, Vyash, additional, Stark, Craig E.L., additional, Tran, Tammy T, additional, Wang, Lei, additional, Yushkevich, Paul A., additional, Amunts, Katrin, additional, Augustinack, Jean, additional, Ding, Song‐Lin, additional, Insausti, Ricardo, additional, Kedo, Olga, additional, Berron, David, additional, and Wisse, Laura EM, additional

Published
2023
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22. Characterizing the human hippocampus in aging and Alzheimer’s disease using a computational atlas derived from ex vivo MRI and histology

Author

Adler, Daniel H., Wisse, Laura E. M., Ittyerah, Ranjit, Pluta, John B., Ding, Song-Lin, Xie, Long, Wang, Jiancong, Kadivar, Salmon, Robinson, John L., Schuck, Theresa, Trojanowski, John Q., Grossman, Murray, Detre, John A., Elliott, Mark A., Toledo, Jon B., Liu, Weixia, Pickup, Stephen, Miller, Michael I., Das, Sandhitsu R., Wolk, David A., and Yushkevich, Paul A.

Published
2018

23. Classification of electrophysiological and morphological neuron types in the mouse visual cortex

Author

Gouwens, Nathan W., Sorensen, Staci A., Berg, Jim, Lee, Changkyu, Jarsky, Tim, Ting, Jonathan, Sunkin, Susan M., Feng, David, Anastassiou, Costas A., Barkan, Eliza, Bickley, Kris, Blesie, Nicole, Braun, Thomas, Brouner, Krissy, Budzillo, Agata, Caldejon, Shiella, Casper, Tamara, Castelli, Dan, Chong, Peter, Crichton, Kirsten, Cuhaciyan, Christine, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Desta, Tsega, Ding, Song-Lin, Dingman, Samuel, Doperalski, Alyse, Dotson, Nadezhda, Egdorf, Tom, Fisher, Michael, de Frates, Rebecca A., Garren, Emma, Garwood, Marissa, Gary, Amanda, Gaudreault, Nathalie, Godfrey, Keith, Gorham, Melissa, Gu, Hong, Habel, Caroline, Hadley, Kristen, Harrington, James, Harris, Julie A., Henry, Alex, Hill, DiJon, Josephsen, Sam, Kebede, Sara, Kim, Lisa, Kroll, Matthew, Lee, Brian, Lemon, Tracy, Link, Katherine E., Liu, Xiaoxiao, Long, Brian, Mann, Rusty, McGraw, Medea, Mihalas, Stefan, Mukora, Alice, Murphy, Gabe J., Ng, Lindsay, Ngo, Kiet, Nguyen, Thuc Nghi, Nicovich, Philip R., Oldre, Aaron, Park, Daniel, Parry, Sheana, Perkins, Jed, Potekhina, Lydia, Reid, David, Robertson, Miranda, Sandman, David, Schroedter, Martin, Slaughterbeck, Cliff, Soler-Llavina, Gilberto, Sulc, Josef, Szafer, Aaron, Tasic, Bosiljka, Taskin, Naz, Teeter, Corinne, Thatra, Nivretta, Tung, Herman, Wakeman, Wayne, Williams, Grace, Young, Rob, Zhou, Zhi, Farrell, Colin, Peng, Hanchuan, Hawrylycz, Michael J., Lein, Ed, Ng, Lydia, Arkhipov, Anton, Bernard, Amy, Phillips, John W., Zeng, Hongkui, and Koch, Christof

Published
2019
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24. Author Correction: Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

Bakken, Trygve E., Jorstad, Nikolas L., Hu, Qiwen, Lake, Blue B., Tian, Wei, Kalmbach, Brian E., Crow, Megan, Hodge, Rebecca D., Krienen, Fenna M., Sorensen, Staci A., Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D., Aldridge, Andrew I., Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G., Crichton, Kirsten, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T., Herb, Brian R., Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S., Liu, Hanqing, Lucero, Jacinta D., Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A., Moussa, Marmar, Nery, Joseph R., Nicovich, Philip R., Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K., Owen, Scott, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M., Rimorin, Christine, Rivkin, Angeline, Romanow, William J., Sedeño-Cortés, Adriana E., Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A., Behrens, M. Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R., Höllt, Thomas, Horwitz, Gregory D., Keene, C. Dirk, Kharchenko, Peter V., Ko, Andrew L., Lelieveldt, Boudewijn P., Luo, Chongyuan, Mukamel, Eran A., Pinto-Duarte, António, Preiss, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H., Smith, Kimberly, Spain, William J., White, Owen R., Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z., McCarroll, Steven A., Ting, Jonathan T., Zeng, Hongkui, Zhang, Kun, Feng, Guoping, Ecker, Joseph R., Linnarsson, Sten, and Lein, Ed S.

Published
2022
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25. Single-cell DNA methylation and 3D genome architecture in the human brain

Author

Tian, Wei, primary, Zhou, Jingtian, additional, Bartlett, Anna, additional, Zeng, Qiurui, additional, Liu, Hanqing, additional, Castanon, Rosa G., additional, Kenworthy, Mia, additional, Altshul, Jordan, additional, Valadon, Cynthia, additional, Aldridge, Andrew, additional, Nery, Joseph R., additional, Chen, Huaming, additional, Xu, Jiaying, additional, Johnson, Nicholas D., additional, Lucero, Jacinta, additional, Osteen, Julia K., additional, Emerson, Nora, additional, Rink, Jon, additional, Lee, Jasper, additional, Li, Yang E., additional, Siletti, Kimberly, additional, Liem, Michelle, additional, Claffey, Naomi, additional, O’Connor, Carolyn, additional, Yanny, Anna Marie, additional, Nyhus, Julie, additional, Dee, Nick, additional, Casper, Tamara, additional, Shapovalova, Nadiya, additional, Hirschstein, Daniel, additional, Ding, Song-Lin, additional, Hodge, Rebecca, additional, Levi, Boaz P., additional, Keene, C. Dirk, additional, Linnarsson, Sten, additional, Lein, Ed, additional, Ren, Bing, additional, Behrens, M. Margarita, additional, and Ecker, Joseph R., additional

Published
2023
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26. Transcriptomic cytoarchitecture reveals principles of human neocortex organization

Author

Jorstad, Nikolas L., primary, Close, Jennie, additional, Johansen, Nelson, additional, Yanny, Anna Marie, additional, Barkan, Eliza R., additional, Travaglini, Kyle J., additional, Bertagnolli, Darren, additional, Campos, Jazmin, additional, Casper, Tamara, additional, Crichton, Kirsten, additional, Dee, Nick, additional, Ding, Song-Lin, additional, Gelfand, Emily, additional, Goldy, Jeff, additional, Hirschstein, Daniel, additional, Kiick, Katelyn, additional, Kroll, Matthew, additional, Kunst, Michael, additional, Lathia, Kanan, additional, Long, Brian, additional, Martin, Naomi, additional, McMillen, Delissa, additional, Pham, Trangthanh, additional, Rimorin, Christine, additional, Ruiz, Augustin, additional, Shapovalova, Nadiya, additional, Shehata, Soraya, additional, Siletti, Kimberly, additional, Somasundaram, Saroja, additional, Sulc, Josef, additional, Tieu, Michael, additional, Torkelson, Amy, additional, Tung, Herman, additional, Callaway, Edward M., additional, Hof, Patrick R., additional, Keene, C. Dirk, additional, Levi, Boaz P., additional, Linnarsson, Sten, additional, Mitra, Partha P., additional, Smith, Kimberly, additional, Hodge, Rebecca D., additional, Bakken, Trygve E., additional, and Lein, Ed S, additional

Published
2023
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27. Transcriptomic diversity of cell types across the adult human brain

Author

Siletti, Kimberly, primary, Hodge, Rebecca, additional, Mossi Albiach, Alejandro, additional, Lee, Ka Wai, additional, Ding, Song-Lin, additional, Hu, Lijuan, additional, Lönnerberg, Peter, additional, Bakken, Trygve, additional, Casper, Tamara, additional, Clark, Michael, additional, Dee, Nick, additional, Gloe, Jessica, additional, Hirschstein, Daniel, additional, Shapovalova, Nadiya V., additional, Keene, C. Dirk, additional, Nyhus, Julie, additional, Tung, Herman, additional, Yanny, Anna Marie, additional, Arenas, Ernest, additional, Lein, Ed S., additional, and Linnarsson, Sten, additional

Published
2023
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28. Author Correction: Human neocortical expansion involves glutamatergic neuron diversification

Author

Berg, Jim, Sorensen, Staci A., Ting, Jonathan T., Miller, Jeremy A., Chartrand, Thomas, Buchin, Anatoly, Bakken, Trygve E., Budzillo, Agata, Dee, Nick, Ding, Song-Lin, Gouwens, Nathan W., Hodge, Rebecca D., Kalmbach, Brian, Lee, Changkyu, Lee, Brian R., Alfiler, Lauren, Baker, Katherine, Barkan, Eliza, Beller, Allison, Berry, Kyla, Bertagnolli, Darren, Bickley, Kris, Bomben, Jasmine, Braun, Thomas, Brouner, Krissy, Casper, Tamara, Chong, Peter, Crichton, Kirsten, Dalley, Rachel, de Frates, Rebecca, Desta, Tsega, Lee, Samuel Dingman, D’Orazi, Florence, Dotson, Nadezhda, Egdorf, Tom, Enstrom, Rachel, Farrell, Colin, Feng, David, Fong, Olivia, Furdan, Szabina, Galakhova, Anna A., Gamlin, Clare, Gary, Amanda, Glandon, Alexandra, Goldy, Jeff, Gorham, Melissa, Goriounova, Natalia A., Gratiy, Sergey, Graybuck, Lucas, Gu, Hong, Hadley, Kristen, Hansen, Nathan, Heistek, Tim S., Henry, Alex M., Heyer, Djai B., Hill, DiJon, Hill, Chris, Hupp, Madie, Jarsky, Tim, Kebede, Sara, Keene, Lisa, Kim, Lisa, Kim, Mean-Hwan, Kroll, Matthew, Latimer, Caitlin, Levi, Boaz P., Link, Katherine E., Mallory, Matthew, Mann, Rusty, Marshall, Desiree, Maxwell, Michelle, McGraw, Medea, McMillen, Delissa, Melief, Erica, Mertens, Eline J., Mezei, Leona, Mihut, Norbert, Mok, Stephanie, Molnar, Gabor, Mukora, Alice, Ng, Lindsay, Ngo, Kiet, Nicovich, Philip R., Nyhus, Julie, Olah, Gaspar, Oldre, Aaron, Omstead, Victoria, Ozsvar, Attila, Park, Daniel, Peng, Hanchuan, Pham, Trangthanh, Pom, Christina A., Potekhina, Lydia, Rajanbabu, Ramkumar, Ransford, Shea, Reid, David, Rimorin, Christine, Ruiz, Augustin, Sandman, David, Sulc, Josef, Sunkin, Susan M., Szafer, Aaron, Szemenyei, Viktor, Thomsen, Elliot R., Tieu, Michael, Torkelson, Amy, Trinh, Jessica, Tung, Herman, Wakeman, Wayne, Waleboer, Femke, Ward, Katelyn, Wilbers, René, Williams, Grace, Yao, Zizhen, Yoon, Jae-Geun, Anastassiou, Costas, Arkhipov, Anton, Barzo, Pal, Bernard, Amy, Cobbs, Charles, de Witt Hamer, Philip C., Ellenbogen, Richard G., Esposito, Luke, Ferreira, Manuel, Gwinn, Ryder P., Hawrylycz, Michael J., Hof, Patrick R., Idema, Sander, Jones, Allan R., Keene, C. Dirk, Ko, Andrew L., Murphy, Gabe J., Ng, Lydia, Ojemann, Jeffrey G., Patel, Anoop P., Phillips, John W., Silbergeld, Daniel L., Smith, Kimberly, Tasic, Bosiljka, Yuste, Rafael, Segev, Idan, de Kock, Christiaan P. J., Mansvelder, Huibert D., Tamas, Gabor, Zeng, Hongkui, Koch, Christof, and Lein, Ed S.

Published
2022
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30. A novel subdivision of the bed nucleus of stria terminalis in monkey, rat, and mouse brains.

Author

Ding, Song‐Lin

Abstract

The bed nucleus of stria terminalis (BST) is a critical structure that mediates sustained vigilant responses to contextual, diffuse, and unpredictable threats. Dysfunction of the BST could lead to excessive anxiety and hypervigilance, which are often observed in posttraumatic stress disorder and anxiety disorders. Vigilance of potential future threats from the external environment is a basic brain function and probably requires rapid and/or short neural circuits, which enable both quick detection of the potential threats and fast adaptive responses. However, the BST in literature does not appear to receive spatial information directly from earlier visual or spatial processing structures. In this study, a novel subdivision of the BST is uncovered in monkey, rat, and mouse brains based on the human equivalent and is found in mouse to receive direct inputs from the ventral lateral geniculate nucleus and pretectal nucleus as well as from the spatial processing structures such as subiculum, presubiculum, and medial entorhinal cortex. This new subdivision, termed spindle‐shaped small cell subdivision (BSTsc), is located between the known BST and the anterior thalamus. In addition to the unique afferent connections and cell morphology, the BSTsc also displays unique molecular signature (e.g., positive for excitatory markers) compared with other BST subdivisions, which are mostly composed of inhibitory GABAergic neurons. The BSTsc appears to have largely overlapping efferent projections with other BST subdivisions such as the projections to the amygdala, hypothalamus, nucleus accumbens, septum, and brainstem. Together, the present study suggests that the BSTsc is poised to serve as a shortcut bridge directly linking spatial information from the environment to vigilant adaptive internal responses. [ABSTRACT FROM AUTHOR]

Published
2023
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31. Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

Author

Wuestefeld, Anika, primary, Baumeister, Hannah, additional, Adams, Jenna N, additional, de Flores, Robin, additional, Hodgetts, Carl, additional, Mazloum-Farzaghi, Negar, additional, Olsen, Rosanna K, additional, Puliyadi, Vyash, additional, Tran, Tammy T, additional, Bakker, Arnold, additional, Canada, Kelsey L, additional, Dalton, Marshall A, additional, Daugherty, Ana M, additional, La Joie, Renaud, additional, Wang, Lei, additional, Bedard, Madigan, additional, Buendia, Esther, additional, Denning, Amanda, additional, Irwin, David J, additional, Ittyerah, Ranjit, additional, Lee, Edward B, additional, Lim, Sydney, additional, Iniguez de Onzono Martin, Maria Mercedes, additional, Munoz Lopez, Monica, additional, Schuck, Theresa, additional, Trotman, Winifred, additional, Vela, Alicia, additional, Yushkevich, Paul, additional, Amunts, Karin, additional, Augustinack, Jean C, additional, Ding, Song-Lin, additional, Insausti, Ricardo, additional, Kedo, Olga, additional, Berron, David, additional, and Wisse, Laura E M, additional

Published
2023
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32. Integrated multimodal cell atlas of Alzheimer’s disease

Author

Gabitto, Mariano, primary, Travaglini, Kyle, additional, Ariza, Jeannelle, additional, Kaplan, Eitan, additional, Long, Brian, additional, Rachleff, Victoria, additional, Ding, Yi, additional, Mahoney, Joseph, additional, Dee, Nick, additional, Goldy, Jeff, additional, Melief, Erica, additional, Brouner, Krissy, additional, Compos, Jazmin, additional, Campos, John, additional, Carr, Ambrose, additional, Casper, Tamara, additional, Chakrabarty, Rushil, additional, Clark, Michael, additional, Cool, Jonah, additional, Dalley, Rachel, additional, Darvas, Martin, additional, Dolbeare, Tim, additional, Ding, Song-Lin, additional, Egdorf, Tom, additional, Esposito, Luke, additional, Ferrer, Rebecca, additional, Gala, Rohan, additional, Gary, Amanda, additional, Gloe, Jessica, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Ho, Windy, additional, Jarsky, Tim, additional, Johansen, Nelson, additional, Kalmbach, Brian, additional, Keene, Lisa, additional, Khawand, Sarah, additional, Kilgore, Mitchell, additional, Kirkland, Amanda, additional, Kunst, Michael, additional, Lee, Brian, additional, Donald, Christine Mac, additional, Malone, Jocelin, additional, Maltzer, Zoe, additional, Martin, Naomi, additional, McCue, Rachel, additional, McMillen, Delissa, additional, Meyerdierks, Emma, additional, Meyers, Kelly, additional, Mollenkopf, Tyler, additional, Montine, Mark, additional, Nolan, Amber, additional, Nyhus, Julie, additional, Olsen, Paul, additional, Pacleb, Maiya, additional, Pham, Trangthanh, additional, Pom, Christina, additional, Postupna, Nadia, additional, Ruiz, Augustin, additional, Schantz, Aimee, additional, Sorensen, Staci, additional, Staats, Brian, additional, Sullivan, Matt, additional, Sunkin, Susan, additional, Thompson, Carol, additional, Tieu, Michael, additional, Ting, Jonathan, additional, Torkelson, Amy, additional, Tran, Tracy, additional, Cuevas, Nasmil Valera, additional, Wang, Ming-Qiang, additional, Waters, Jack, additional, Wilson, Angela, additional, Haynor, David, additional, Gatto, Nicole, additional, Jayadev, Suman, additional, Mufti, Shoaib, additional, Ng, Lydia, additional, Mukherjee, Shubhabrata, additional, Crane, Paul, additional, Latimer, Caitlin, additional, Levi, Boaz, additional, Smith, Kimberly, additional, Close, Jennie, additional, Miller, Jeremy, additional, Hodge, Rebecca, additional, Larson, Eric, additional, Grabowski, Thomas, additional, Hawrylycz, Michael, additional, Keene, C., additional, and Lein, Ed, additional

Published
2023
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33. Integrated multimodal cell atlas of Alzheimer’s disease

Author

Gabitto, Mariano I., primary, Travaglini, Kyle J., additional, Rachleff, Victoria M., additional, Kaplan, Eitan S., additional, Long, Brian, additional, Ariza, Jeanelle, additional, Ding, Yi, additional, Mahoney, Joseph T., additional, Dee, Nick, additional, Goldy, Jeff, additional, Melief, Erica J., additional, Brouner, Krissy, additional, Campos, Jazmin, additional, Campos, John, additional, Carr, Ambrose J., additional, Casper, Tamara, additional, Chakrabarty, Rushil, additional, Clark, Michael, additional, Cool, Jonah, additional, Valera Cuevas, Nasmil J., additional, Dalley, Rachel, additional, Darvas, Martin, additional, Ding, Song-Lin, additional, Dolbeare, Tim, additional, Mac Donald, Christine L., additional, Egdorf, Tom, additional, Esposito, Luke, additional, Ferrer, Rebecca, additional, Gala, Rohan, additional, Gary, Amanda, additional, Gloe, Jessica, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Hirschstein, Daniel, additional, Ho, Windy, additional, Jarksy, Tim, additional, Johansen, Nelson, additional, Kalmbach, Brian E., additional, Keene, Lisa M., additional, Khawand, Sarah, additional, Kilgore, Mitch, additional, Kirkland, Amanda, additional, Kunst, Michael, additional, Lee, Brian R., additional, Malone, Jocelin, additional, Maltzer, Zoe, additional, Martin, Naomi, additional, McCue, Rachel, additional, McMillen, Delissa, additional, Meyerdierks, Emma, additional, Meyers, Kelly P., additional, Mollenkopf, Tyler, additional, Montine, Mark, additional, Nolan, Amber L., additional, Nyhus, Julie, additional, Olsen, Paul A., additional, Pacleb, Maiya, additional, Peña, Nicholas, additional, Pham, Thanh, additional, Pom, Christina Alice, additional, Postupna, Nadia, additional, Ruiz, Augustin, additional, Schantz, Aimee M., additional, Shapovalova, Nadiya V., additional, Sorensen, Staci A., additional, Staats, Brian, additional, Sullivan, Matt, additional, Sunkin, Susan M., additional, Thompson, Carol, additional, Tieu, Michael, additional, Ting, Jonathan, additional, Torkelson, Amy, additional, Tran, Tracy, additional, Wang, Ming-Qiang, additional, Waters, Jack, additional, Wilson, Angela M., additional, Haynor, David, additional, Gatto, Nicole, additional, Jayadev, Suman, additional, Mufti, Shoaib, additional, Ng, Lydia, additional, Mukherjee, Shubhabrata, additional, Crane, Paul K., additional, Latimer, Caitlin S., additional, Levi, Boaz P., additional, Smith, Kimberly, additional, Close, Jennie L., additional, Miller, Jeremy A., additional, Hodge, Rebecca D., additional, Larson, Eric B., additional, Grabowski, Thomas J., additional, Hawrylycz, Michael, additional, Dirk Keene, C., additional, and Lein, Ed S., additional

Published
2023
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34. Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: Towards a harmonized segmentation protocol

Author

Yushkevich, Paul A., Amaral, Robert S.C., Augustinack, Jean C., Bender, Andrew R., Bernstein, Jeffrey D., Boccardi, Marina, Bocchetta, Martina, Burggren, Alison C., Carr, Valerie A., Chakravarty, M. Mallar, Chételat, Gaël, Daugherty, Ana M., Davachi, Lila, Ding, Song-Lin, Ekstrom, Arne, Geerlings, Mirjam I., Hassan, Abdul, Huang, Yushan, Iglesias, J. Eugenio, La Joie, Renaud, Kerchner, Geoffrey A., LaRocque, Karen F., Libby, Laura A., Malykhin, Nikolai, Mueller, Susanne G., Olsen, Rosanna K., Palombo, Daniela J., Parekh, Mansi B., Pluta, John B., Preston, Alison R., Pruessner, Jens C., Ranganath, Charan, Raz, Naftali, Schlichting, Margaret L., Schoemaker, Dorothee, Singh, Sachi, Stark, Craig E.L., Suthana, Nanthia, Tompary, Alexa, Turowski, Marta M., Van Leemput, Koen, Wagner, Anthony D., Wang, Lei, Winterburn, Julie L., Wisse, Laura E.M., Yassa, Michael A., and Zeineh, Michael M.

Published
2015
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35. Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

Author

Wuestefeld, Anika, Baumeister, Hannah, Canada, Kelsey L., Dalton, Marshall A., Daugherty, Ana M., Joie, Renaud La, Wang, Lei, Bedard, Madigan, Buendia, Esther, Denning, Amanda, del Mar Arroyo-Jiménez, María, Artacho-Pérula, Emilio, Adams, Jenna N., Irwin, David J., Ittyerah, Ranjit, Lee, Edward B., Lim, Sydney, del Pilar Marcos-Rabal, María, de Onzoño Martin, Maria Mercedes Iñiguez, Lopez, Monica Munoz, de la Rosa Prieto, Carlos, Schuck, Theresa, Trotman, Winifred, de Flores, Robin, Vela, Alicia, Yushkevich, Paul, Amunts, Katrin, Augustinack, Jean C., Ding, Song-Lin, Insausti, Ricardo, Kedo, Olga, Berron, David, Wisse, Laura E. M., Hodgetts, Carl, Mazloum-Farzaghi, Negar, Olsen, Rosanna K., Puliyadi, Vyash, Tran, Tammy T., and Bakker, Arnold

Subjects
ddc:570, Article
Abstract

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer’s disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations.Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 µm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail.Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists’ agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually.The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.

Published
2023
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36. Automatic Clustering and Thickness Measurement of Anatomical Variants of the Human Perirhinal Cortex

Author

Xie, Long, Pluta, John, Wang, Hongzhi, Das, Sandhitsu R., Mancuso, Lauren, Kliot, Dasha, Avants, Brian B., Ding, Song-Lin, Wolk, David A., Yushkevich, Paul A., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Kobsa, Alfred, Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Golland, Polina, editor, Hata, Nobuhiko, editor, Barillot, Christian, editor, Hornegger, Joachim, editor, and Howe, Robert, editor

Published
2014
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40. Transcriptomic cytoarchitecture reveals principles of human neocortex organization

Author

Jorstad, Nikolas L., primary, Close, Jennie, additional, Johansen, Nelson, additional, Yanny, Anna Marie, additional, Barkan, Eliza R., additional, Travaglini, Kyle J., additional, Bertagnolli, Darren, additional, Campos, Jazmin, additional, Casper, Tamara, additional, Crichton, Kirsten, additional, Dee, Nick, additional, Ding, Song-Lin, additional, Gelfand, Emily, additional, Goldy, Jeff, additional, Hirschstein, Daniel, additional, Kroll, Matthew, additional, Kunst, Michael, additional, Lathia, Kanan, additional, Long, Brian, additional, Martin, Naomi, additional, McMillen, Delissa, additional, Pham, Trangthanh, additional, Rimorin, Christine, additional, Ruiz, Augustin, additional, Shapovalova, Nadiya, additional, Shehata, Soraya, additional, Siletti, Kimberly, additional, Somasundaram, Saroja, additional, Sulc, Josef, additional, Tieu, Michael, additional, Torkelson, Amy, additional, Tung, Herman, additional, Ward, Katelyn, additional, Callaway, Edward M., additional, Hof, Patrick R., additional, Keene, C. Dirk, additional, Levi, Boaz P., additional, Linnarsson, Sten, additional, Mitra, Partha P., additional, Smith, Kimberly, additional, Hodge, Rebecca D., additional, Bakken, Trygve E., additional, and Lein, Ed S., additional

Published
2022
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41. Transcriptomic diversity of cell types across the adult human brain

Author

Siletti, Kimberly, primary, Hodge, Rebecca, additional, Mossi Albiach, Alejandro, additional, Hu, Lijuan, additional, Lee, Ka Wai, additional, Lönnerberg, Peter, additional, Bakken, Trygve, additional, Ding, Song-Lin, additional, Clark, Michael, additional, Casper, Tamara, additional, Dee, Nick, additional, Gloe, Jessica, additional, Keene, C. Dirk, additional, Nyhus, Julie, additional, Tung, Herman, additional, Yanny, Anna Marie, additional, Arenas, Ernest, additional, Lein, Ed S., additional, and Linnarsson, Sten, additional

Published
2022
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42. Comparative transcriptomics reveals human-specific cortical features

Author

Jorstad, Nikolas L., primary, Song, Janet H.T., additional, Exposito-Alonso, David, additional, Suresh, Hamsini, additional, Castro, Nathan, additional, Krienen, Fenna M., additional, Yanny, Anna Marie, additional, Close, Jennie, additional, Gelfand, Emily, additional, Travaglini, Kyle J., additional, Basu, Soumyadeep, additional, Beaudin, Marc, additional, Bertagnolli, Darren, additional, Crow, Megan, additional, Ding, Song-Lin, additional, Eggermont, Jeroen, additional, Glandon, Alexandra, additional, Goldy, Jeff, additional, Kroes, Thomas, additional, Long, Brian, additional, McMillen, Delissa, additional, Pham, Trangthanh, additional, Rimorin, Christine, additional, Siletti, Kimberly, additional, Somasundaram, Saroja, additional, Tieu, Michael, additional, Torkelson, Amy, additional, Ward, Katelyn, additional, Feng, Guoping, additional, Hopkins, William D., additional, Höllt, Thomas, additional, Keene, C. Dirk, additional, Linnarsson, Sten, additional, McCarroll, Steven A., additional, Lelieveldt, Boudewijn P., additional, Sherwood, Chet C., additional, Smith, Kimberly, additional, Walsh, Christopher A., additional, Dobin, Alexander, additional, Gillis, Jesse, additional, Lein, Ed S., additional, Hodge, Rebecca D., additional, and Bakken, Trygve E., additional

Published
2022
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43. Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

Bakken, Trygve E., Jorstad, Nikolas L., Hu, Qiwen, Lake, Blue B., Tian, Wei, Kalmbach, Brian E., Crow, Megan, Hodge, Rebecca D., Krienen, Fenna M., Sorensen, Staci A., Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D., Aldridge, Andrew I., Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G., Crichton, Kirsten, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T., Herb, Brian R., Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S., Liu, Hanqing, Lucero, Jacinta D., Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A., Moussa, Marmar, Nery, Joseph R., Nicovich, Philip R., Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K., Owen, Scott, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M., Rimorin, Christine, Rivkin, Angeline, Romanow, William J., Sedeño-Cortés, Adriana E., Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A., Behrens, M. Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R., Höllt, Thomas, Horwitz, Gregory D., Keene, C. Dirk, Kharchenko, Peter V., Ko, Andrew L., Lelieveldt, Boudewijn P., Luo, Chongyuan, Mukamel, Eran A., Pinto-Duarte, António, Preissl, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H., Smith, Kimberly, Spain, William J., White, Owen R., Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z., McCarroll, Steven A., Ting, Jonathan T., Zeng, Hongkui, Zhang, Kun, Feng, Guoping, Ecker, Joseph R., Linnarsson, Sten, Lein, Ed S., Bakken, Trygve E., Jorstad, Nikolas L., Hu, Qiwen, Lake, Blue B., Tian, Wei, Kalmbach, Brian E., Crow, Megan, Hodge, Rebecca D., Krienen, Fenna M., Sorensen, Staci A., Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D., Aldridge, Andrew I., Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G., Crichton, Kirsten, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T., Herb, Brian R., Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S., Liu, Hanqing, Lucero, Jacinta D., Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A., Moussa, Marmar, Nery, Joseph R., Nicovich, Philip R., Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K., Owen, Scott, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M., Rimorin, Christine, Rivkin, Angeline, Romanow, William J., Sedeño-Cortés, Adriana E., Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A., Behrens, M. Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R., Höllt, Thomas, Horwitz, Gregory D., Keene, C. Dirk, Kharchenko, Peter V., Ko, Andrew L., Lelieveldt, Boudewijn P., Luo, Chongyuan, Mukamel, Eran A., Pinto-Duarte, António, Preissl, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H., Smith, Kimberly, Spain, William J., White, Owen R., Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z., McCarroll, Steven A., Ting, Jonathan T., Zeng, Hongkui, Zhang, Kun, Feng, Guoping, Ecker, Joseph R., Linnarsson, Sten, and Lein, Ed S.

Abstract

AbstractThe primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Published
2022

44. Editorial: 15 years of frontiers in neuroanatomy: the circuits behind the visual cortex.

Author

Takahata, Toru and Ding, Song-Lin

Subjects
VISUAL cortex, CORPUS callosum, OPTICAL information processing, VISUAL pathways, MOTOR cortex, SUPERIOR colliculus, NEUROANATOMY
Abstract

The editorial "15 years of frontiers in neuroanatomy: the circuits behind the visual cortex" presents four original research articles focusing on novel neuroanatomical concepts related to the visual system. The studies explore how the brain in mice connects visual information to movement, how fibers in the brain's corpus callosum are organized, how the primary visual cortex connects to different types of cells in the superior colliculus, and how different areas of the brain in macaques process visual information from the fovea. These findings deepen our understanding of how visual information is processed in the brain and offer insights into potential disruptions in disease. The research contributes to advancing the field of neuroanatomy and visual neuroscience. [Extracted from the article]

Published
2024
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48. Author Correction:Human neocortical expansion involves glutamatergic neuron diversification (Nature, (2021), 598, 7879, (151-158), 10.1038/s41586-021-03813-8)

Author

Berg, Jim, Sorensen, Staci A., Ting, Jonathan T., Miller, Jeremy A., Chartrand, Thomas, Buchin, Anatoly, Bakken, Trygve E., Budzillo, Agata, Dee, Nick, Ding, Song-Lin, Gouwens, Nathan W., Hodge, Rebecca D., Kalmbach, Brian, Lee, Changkyu, Lee, Brian R., Alfiler, Lauren, Baker, Katherine, Barkan, Eliza, Beller, Allison, Berry, Kyla, Bertagnolli, Darren, Bickley, Kris, Bomben, Jasmine, Braun, Thomas, Brouner, Krissy, Casper, Tamara, Chong, Peter, Crichton, Kirsten, Dalley, Rachel, de Frates, Rebecca, Desta, Tsega, Lee, Samuel Dingman, D’Orazi, Florence, Dotson, Nadezhda, Egdorf, Tom, Enstrom, Rachel, Farrell, Colin, Feng, David, Fong, Olivia, Furdan, Szabina, Galakhova, Anna A., Gamlin, Clare, Gary, Amanda, Glandon, Alexandra, Goldy, Jeff, Gorham, Melissa, Goriounova, Natalia A., Gratiy, Sergey, Graybuck, Lucas, Gu, Hong, Hadley, Kristen, Hansen, Nathan, Heistek, Tim S., Henry, Alex M., Heyer, Djai B., Hill, DiJon, Hill, Chris, Hupp, Madie, Jarsky, Tim, Kebede, Sara, Keene, Lisa, Kim, Lisa, Kim, Mean-Hwan, Kroll, Matthew, Latimer, Caitlin, Levi, Boaz P., Link, Katherine E., Mallory, Matthew, Mann, Rusty, Marshall, Desiree, Maxwell, Michelle, McGraw, Medea, McMillen, Delissa, Melief, Erica, Mertens, Eline J., Mezei, Leona, Mihut, Norbert, Mok, Stephanie, Molnar, Gabor, Mukora, Alice, Ng, Lindsay, Ngo, Kiet, Nicovich, Philip R., Nyhus, Julie, Olah, Gaspar, Oldre, Aaron, Omstead, Victoria, Ozsvar, Attila, Park, Daniel, Peng, Hanchuan, Pham, Trangthanh, Pom, Christina A., Potekhina, Lydia, Rajanbabu, Ramkumar, Ransford, Shea, Reid, David, Rimorin, Christine, Ruiz, Augustin, Sandman, David, Sulc, Josef, Sunkin, Susan M., Szafer, Aaron, Szemenyei, Viktor, Thomsen, Elliot R., Tieu, Michael, Torkelson, Amy, Trinh, Jessica, Tung, Herman, Wakeman, Wayne, Waleboer, Femke, Ward, Katelyn, Wilbers, René, Williams, Grace, Yao, Zizhen, Yoon, Jae-Geun, Anastassiou, Costas, Arkhipov, Anton, Barzo, Pal, Bernard, Amy, Cobbs, Charles, de Witt Hamer, Philip C., Ellenbogen, Richard G., Esposito, Luke, Ferreira, Manuel, Gwinn, Ryder P., Hawrylycz, Michael J., Hof, Patrick R., Idema, Sander, Jones, Allan R., Keene, C. Dirk, Ko, Andrew L., Murphy, Gabe J., Ng, Lydia, Ojemann, Jeffrey G., Patel, Anoop P., Phillips, John W., Silbergeld, Daniel L., Smith, Kimberly, Tasic, Bosiljka, Yuste, Rafael, Segev, Idan, de Kock, Christiaan P. J., Mansvelder, Huibert D., Tamas, Gabor, Zeng, Hongkui, Koch, Christof, and Lein, Ed S.

Abstract

In the version of this Article initially published, the Acknowledgements statement contained an error. Originally appearing with thanks for support given in part as follows, “R01EY023173 from The National Eye Institute, U01MH105982 from the National Institute of Mental Health and Eunice Kennedy Shriver National Institute of Child Health and Human Development, and R011EY023173 from The National Institute of Allergy and Infectious Disease,” the last number (R011EY023173) was mistakenly added and is not in fact a grant or one provided by the NIAID. The mention has been removed. The changes have been made to the online version of the Article.

Published
2022
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49. Comprehensive cellular‐resolution atlas of the adult human brain

Author

Ding, Song‐Lin, Royall, Joshua J., Sunkin, Susan M., Ng, Lydia, Facer, Benjamin A.C., Lesnar, Phil, Guillozet‐Bongaarts, Angie, McMurray, Bergen, Szafer, Aaron, Dolbeare, Tim A., Stevens, Allison, Tirrell, Lee, Benner, Thomas, Caldejon, Shiella, Dalley, Rachel A., Dee, Nick, Lau, Christopher, Nyhus, Julie, Reding, Melissa, Riley, Zackery L., Sandman, David, Shen, Elaine, van der Kouwe, Andre, Varjabedian, Ani, Write, Michelle, Zollei, Lilla, Dang, Chinh, Knowles, James A., Koch, Christof, Phillips, John W., Sestan, Nenad, Wohnoutka, Paul, Zielke, H. Ronald, Hohmann, John G., Jones, Allan R., Bernard, Amy, Hawrylycz, Michael J., Hof, Patrick R., Fischl, Bruce, and LeinReference, Ed S.

Published
2017
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50. A multimodal cell census and atlas of the mammalian primary motor cortex

Author

Callaway, Edward M., Dong, Hong-Wei, Ecker, Joseph R., Hawrylycz, Michael J., Huang, Z. Josh, Lein, Ed S., Ngai, John, Osten, Pavel, Ren, Bing, Tolias, Andreas Savas, White, Owen, Zeng, Hongkui, Zhuang, Xiaowei, Ascoli, Giorgio A., Behrens, M. Margarita, Chun, Jerold, Feng, Guoping, Gee, James C., Ghosh, Satrajit S., Halchenko, Yaroslav O., Hertzano, Ronna, Lim, Byung Kook, Martone, Maryann E., Ng, Lydia, Pachter, Lior, Ropelewski, Alexander J., Tickle, Timothy L., Yang, X. William, Zhang, Kun, Bakken, Trygve E., Berens, Philipp, Daigle, Tanya L., Harris, Julie A., Jorstad, Nikolas L., Kalmbach, Brian E., Kobak, Dmitry, Li, Yang Eric, Liu, Hanqing, Matho, Katherine S., Mukamel, Eran A., Naeemi, Maitham, Scala, Federico, Tan, Pengcheng, Ting, Jonathan T., Xie, Fangming, Zhang, Meng, Zhang, Zhuzhu, Zhou, Jingtian, Zingg, Brian, Armand, Ethan, Yao, Zizhen, Bertagnolli, Darren, Casper, Tamara, Crichton, Kirsten, Dee, Nick, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Dougherty, Elizabeth L., Fong, Olivia, Goldman, Melissa, Goldy, Jeff, Hodge, Rebecca D., Hu, Lijuan, Keene, C. Dirk, Krienen, Fenna M., Kroll, Matthew, Lake, Blue B., Lathia, Kanan, Linnarsson, Sten, Liu, Christine S., Macosko, Evan Z., McCarroll, Steven A., McMillen, Delissa, Nadaf, Naeem M., Nguyen, Thuc Nghi, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Reed, Nora M., Regev, Aviv, Rimorin, Christine, Romanow, William J., Savoia, Steven, Siletti, Kimberly, Smith, Kimberly, Sulc, Josef, Tasic, Bosiljka, Tieu, Michael, Torkelson, Amy, Tung, Herman, van Velthoven, Cindy T. J., Vanderburg, Charles R., Yanny, Anna Marie, Fang, Rongxin, Hou, Xiaomeng, Lucero, Jacinta D., Osteen, Julia K., Pinto-Duarte, Antonio, Poirion, Olivier, Preissl, Sebastian, Wang, Xinxin, Aldridge, Andrew I., Bartlett, Anna, Boggeman, Lara, O’Connor, Carolyn, Castanon, Rosa G., Chen, Huaming, Fitzpatrick, Conor, Luo, Chongyuan, Nery, Joseph R., Nunn, Michael, Rivkin, Angeline C., Tian, Wei, Dominguez, Bertha, Ito-Cole, Tony, Jacobs, Matthew, Jin, Xin, Lee, Cheng-Ta, Lee, Kuo-Fen, Miyazaki, Paula Assakura, Pang, Yan, Rashid, Mohammad, Smith, Jared B., Vu, Minh, Williams, Elora, Biancalani, Tommaso, Booeshaghi, A. Sina, Crow, Megan, Dudoit, Sandrine, Fischer, Stephan, Gillis, Jesse, Hu, Qiwen, Kharchenko, Peter V., Niu, Sheng-Yong, Ntranos, Vasilis, Purdom, Elizabeth, Risso, Davide, de Bézieux, Hector Roux, Somasundaram, Saroja, Street, Kelly, Svensson, Valentine, Vaishnav, Eeshit Dhaval, Van den Berge, Koen, Welch, Joshua D., An, Xu, Bateup, Helen S., Bowman, Ian, Chance, Rebecca K., Foster, Nicholas N., Galbavy, William, Gong, Hui, Gou, Lin, Hatfield, Joshua T., Hintiryan, Houri, Hirokawa, Karla E., Kim, Gukhan, Kramer, Daniel J., Li, Anan, Li, Xiangning, Luo, Qingming, Muñoz-Castañeda, Rodrigo, Stafford, David A., Feng, Zhao, Jia, Xueyan, Jiang, Shengdian, Jiang, Tao, Kuang, Xiuli, Larsen, Rachael, Lesnar, Phil, Li, Yaoyao, Li, Yuanyuan, Liu, Lijuan, Peng, Hanchuan, Qu, Lei, Ren, Miao, Ruan, Zongcai, Shen, Elise, Song, Yuanyuan, Wakeman, Wayne, Wang, Peng, Wang, Yimin, Wang, Yun, Yin, Lulu, Yuan, Jing, Zhao, Sujun, Zhao, Xuan, Narasimhan, Arun, Palaniswamy, Ramesh, Banerjee, Samik, Ding, Liya, Huilgol, Dhananjay, Huo, Bingxing, Kuo, Hsien-Chi, Laturnus, Sophie, Li, Xu, Mitra, Partha P., Mizrachi, Judith, Wang, Quanxin, Xie, Peng, Xiong, Feng, Yu, Yang, Eichhorn, Stephen W., Berg, Jim, Bernabucci, Matteo, Bernaerts, Yves, Cadwell, Cathryn René, Castro, Jesus Ramon, Dalley, Rachel, Hartmanis, Leonard, Horwitz, Gregory D., Jiang, Xiaolong, Ko, Andrew L., Miranda, Elanine, Mulherkar, Shalaka, Nicovich, Philip R., Owen, Scott F., Sandberg, Rickard, Sorensen, Staci A., Tan, Zheng Huan, Allen, Shona, Hockemeyer, Dirk, Lee, Angus Y., Veldman, Matthew B., Adkins, Ricky S., Ament, Seth A., Bravo, Héctor Corrada, Carter, Robert, Chatterjee, Apaala, Colantuoni, Carlo, Crabtree, Jonathan, Creasy, Heather, Felix, Victor, Giglio, Michelle, Herb, Brian R., Kancherla, Jayaram, Mahurkar, Anup, McCracken, Carrie, Nickel, Lance, Olley, Dustin, Orvis, Joshua, Schor, Michael, Hood, Greg, Dichter, Benjamin, Grauer, Michael, Helba, Brian, Bandrowski, Anita, Barkas, Nikolaos, Carlin, Benjamin, D’Orazi, Florence D., Degatano, Kylee, Gillespie, Thomas H., Khajouei, Farzaneh, Konwar, Kishori, Thompson, Carol, Kelly, Kathleen, Mok, Stephanie, Sunkin, Susan, BRAIN Initiative Cell Census Network (BICCN) Corresponding authors, [missing], BICCN contributing principal investigators, [missing], Principal manuscript editors, [missing], Manuscript writing and figure generation, [missing], Analysis coordination, [missing], Integrated data analysis, [missing], scRNA-seq and snRNA-seq data generation and processing, [missing], ATAC-seq data generation and processing, [missing], Methylcytosine data production and analysis, [missing], Epi-retro-seq data generation and processing, [missing], ‘Omics data analysis, [missing], Tracing and connectivity data generation, [missing], Morphology data generation and reconstruction, [missing], OLST/STPT and other data generation, [missing], Morphology, connectivity and imaging analysis, [missing], Spatially resolved single-cell transcriptomics (MERFISH), [missing], Multimodal profiling (Patch-seq), [missing], Transgenic tools, [missing], NeMO archive and analytics, [missing], Brain Image Library (BIL) archive, [missing], DANDI archive, [missing], Brain Cell Data Center (BCDC), [missing], Project management, [missing], and BRAIN Initiative Cell Census Network (BICCN), [missing]

Subjects
Epigenomics, Male, INTERNEURONS, ORGANIZATION, MOUSE, Molecular neuroscience, Neural circuits, CLASSIFICATION, Article, Mice, Atlases as Topic, Glutamates, Species Specificity, Animals, Humans, TRANSCRIPTOMICS, SPECIFICATION, NEURONS, In Situ Hybridization, Fluorescence, Phylogeny, Neurons, Multidisciplinary, Gene Expression Profiling, Biology and Life Sciences, PATHWAYS, Brain, Callithrix, Censuses, Cellular neuroscience, Mathematics and Statistics, SINGLE, Organ Specificity, MORPHOLOGY, Motor cortex, Female, Single-Cell Analysis, Transcriptome
Abstract

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties., The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Published
2021

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