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2. An atlas of healthy and injured cell states and niches in the human kidney.

Author

Lake, Blue, Menon, Rajasree, Winfree, Seth, Hu, Qiwen, Ferreira, Ricardo, Kalhor, Kian, Barwinska, Daria, Otto, Edgar, Ferkowicz, Michael, Diep, Dinh, Plongthongkum, Nongluk, Knoten, Amanda, Urata, Sarah, Mariani, Laura, Naik, Abhijit, Eddy, Sean, Zhang, Bo, Wu, Yan, Salamon, Diane, Williams, James, Wang, Xin, Balderrama, Karol, Hoover, Paul, Murray, Evan, Marshall, Jamie, Noel, Teia, Vijayan, Anitha, Hartman, Austin, Chen, Fei, Waikar, Sushrut, Rosas, Sylvia, Wilson, Francis, Palevsky, Paul, Kiryluk, Krzysztof, Sedor, John, Toto, Robert, Parikh, Chirag, Kim, Eric, Satija, Rahul, Greka, Anna, Macosko, Evan, Kharchenko, Peter, Gaut, Joseph, Hodgin, Jeffrey, Eadon, Michael, Dagher, Pierre, El-Achkar, Tarek, Kretzler, Matthias, Jain, Sanjay, and Zhang, Kun

Subjects
Humans, Cell Nucleus, Gene Expression Profiling, Kidney, Kidney Diseases, Transcriptome, Single-Cell Analysis, Case-Control Studies, Imaging, Three-Dimensional
Abstract

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Published
2023

9. A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex

Author

Yao, Zizhen, Liu, Hanqing, Xie, Fangming, Fischer, Stephan, Adkins, Ricky S, Aldridge, Andrew I, Ament, Seth A, Bartlett, Anna, Behrens, M Margarita, Van den Berge, Koen, Bertagnolli, Darren, de Bézieux, Hector Roux, Biancalani, Tommaso, Booeshaghi, A Sina, Bravo, Héctor Corrada, Casper, Tamara, Colantuoni, Carlo, Crabtree, Jonathan, Creasy, Heather, Crichton, Kirsten, Crow, Megan, Dee, Nick, Dougherty, Elizabeth L, Doyle, Wayne I, Dudoit, Sandrine, Fang, Rongxin, Felix, Victor, Fong, Olivia, Giglio, Michelle, Goldy, Jeff, Hawrylycz, Mike, Herb, Brian R, Hertzano, Ronna, Hou, Xiaomeng, Hu, Qiwen, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, Li, Yang Eric, Lucero, Jacinta D, Luo, Chongyuan, Mahurkar, Anup, McMillen, Delissa, Nadaf, Naeem M, Nery, Joseph R, Nguyen, Thuc Nghi, Niu, Sheng-Yong, Ntranos, Vasilis, Orvis, Joshua, Osteen, Julia K, Pham, Thanh, Pinto-Duarte, Antonio, Poirion, Olivier, Preissl, Sebastian, Purdom, Elizabeth, Rimorin, Christine, Risso, Davide, Rivkin, Angeline C, Smith, Kimberly, Street, Kelly, Sulc, Josef, Svensson, Valentine, Tieu, Michael, Torkelson, Amy, Tung, Herman, Vaishnav, Eeshit Dhaval, Vanderburg, Charles R, van Velthoven, Cindy, Wang, Xinxin, White, Owen R, Huang, Z Josh, Kharchenko, Peter V, Pachter, Lior, Ngai, John, Regev, Aviv, Tasic, Bosiljka, Welch, Joshua D, Gillis, Jesse, Macosko, Evan Z, Ren, Bing, Ecker, Joseph R, Zeng, Hongkui, and Mukamel, Eran A

Subjects
Human Genome, Neurosciences, Genetics, Bioengineering, Biotechnology, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Animals, Atlases as Topic, Datasets as Topic, Epigenesis, Genetic, Epigenomics, Female, Gene Expression Profiling, Male, Mice, Motor Cortex, Neurons, Organ Specificity, Reproducibility of Results, Single-Cell Analysis, Transcriptome, General Science & Technology
Abstract

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.

Published
2021

10. 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

12. Research Progress on Animal Models of Intrauterine Growth Restriction

Author

HU Qiwen, BI Zheng, LIU Haiping, DONG Zhihua, ZHUYanlin, and WANG Jinhua

Subjects
animal model, intrauterine growth restriction, research progress, Medicine
Abstract

The occurrence of intrauterine growth restriction (IUGR) may be related to maternal malnutrition, abnormal placental function, immune abnormalities, genetically related problems as well as other diseases, but the mechanism is still unclear. Therefore, the study of IUGR and the development of its animal model are critical issues in obstetrics. IUGR models are mainly based on laboratory rodents, such as mice and rats, and other mammals such as pigs, rabbits and sheep. This article introduced several common IUGR animal models, including nutrition restriction model, high-altitude pregnancy model, natural selection model, and nicotine exposure model, and also described the construction methods of IUGR models and the comparison of their advantages and disadvantages.

Published
2022
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19. Satellite-Based Monitoring of Methane Emissions from China’s Rice Hub

Author

Liang, Ruosi, Zhang, Yuzhong, Hu, Qiwen, Li, Tingting, Li, Shihua, Yuan, Wenping, Xu, Jialu, Zhao, Yujia, Zhang, Peixuan, Chen, Wei, Zhuang, Minghao, Shen, Guofeng, and Chen, Zichong

Abstract

Rice cultivation is one of the major anthropogenic methane sources in China and globally. However, accurately quantifying regional rice methane emissions is often challenging due to highly heterogeneous emission fluxes and limited measurement data. This study attempts to address this issue by quantifying regional methane emissions from rice cultivation with a high-resolution inversion of satellite methane observations from the Tropospheric Monitoring Instrument (TROPOMI). We apply the method to the largest rice-producing province (Heilongjiang) in China for 2021. Our satellite-based estimation finds a rice methane emission of 0.85 (0.69–1.03) Tg a–1from the province or an average emission factor of 22.0 (17.8–26.6) g m–2a–1when normalized by rice paddy areas. The satellite-based analysis reveals a 2 to 4 times lower bias in widely used global and national inventories, which lack up-to-date regional information. The inversion reduces the uncertainty of regional rice emissions by 73% relative to bottom-up estimates based on field flux measurements. The satellite inversion also shows that the highest rice methane emissions occur in June during the tillering stage of rice, decreasing toward ripening, indicating that the predominant water management practice in the region involves drainage and intermittent flooding after initial flooding. Process-based modeling further suggests that this practice can lead to a reduction of methane emissions by more than 50% compared to continuous flooding of rice paddies and natural wetlands.

Published
2024
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25. Optimizing a high‐sensitivity NanoLuc‐based bioluminescence system for in vivo evaluation of antimicrobial treatment

Author

Shang, Weilong, primary, Hu, Zhen, additional, Li, Mengyang, additional, Wang, Yuting, additional, Rao, Yifan, additional, Tan, Li, additional, Chen, Juan, additional, Huang, Xiaonan, additional, Liu, Lu, additional, Liu, He, additional, Guo, Zuwen, additional, Peng, Huagang, additional, Yang, Yi, additional, Hu, Qiwen, additional, Li, Shu, additional, Hu, Xiaomei, additional, Zou, Jiao, additional, and Rao, Xiancai, additional

Published
2023
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27. Mango‐GPP: A Process‐Based Model for Simulating Gross Primary Productivity of Mangrove Ecosystems

Author

Tang, Yuqi, primary, Li, Tingting, additional, Yang, Xiu‐Qun, additional, Chao, Qingchen, additional, Wang, Chunlin, additional, Lai, Derrick Y. F., additional, Liu, Jiangong, additional, Zhu, Xudong, additional, Zhao, Xiaosong, additional, Fan, Xingwang, additional, Zhang, Yiping, additional, Hu, Qiwen, additional, and Qin, Zhangcai, additional

Published
2023
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29. A novel phage endolysin inactivates a wide range of Staphylococcus aureus and eliminates mono- and mixed-species biofilms associated with S. aureus

Author

Rao, Xiancai, primary, Liu, He, additional, Wei, Xuemei, additional, Wang, Zhefen, additional, Huang, Xiaonan, additional, Li, Mengyang, additional, Hu, Zhen, additional, Zhang, Kexin, additional, Hu, Qiwen, additional, Peng, Huagang, additional, Shang, Weilong, additional, Yang, Yi, additional, Wang, Yuting, additional, and Lu, Shuguang, additional

Published
2023
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31. 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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39. Upper cortical layer–driven network impairment in schizophrenia

Author

Batiuk, Mykhailo Y., primary, Tyler, Teadora, additional, Dragicevic, Katarina, additional, Mei, Shenglin, additional, Rydbirk, Rasmus, additional, Petukhov, Viktor, additional, Deviatiiarov, Ruslan, additional, Sedmak, Dora, additional, Frank, Erzsebet, additional, Feher, Virginia, additional, Habek, Nikola, additional, Hu, Qiwen, additional, Igolkina, Anna, additional, Roszik, Lilla, additional, Pfisterer, Ulrich, additional, Garcia-Gonzalez, Diego, additional, Petanjek, Zdravko, additional, Adorjan, Istvan, additional, Kharchenko, Peter V., additional, and Khodosevich, Konstantin, additional

Published
2022
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41. Upper cortical layer-driven network impairment in schizophrenia

Author

Batiuk, Mykhailo Y., Tyler, Teadora, Dragicevic, Katarina, Mei, Shenglin, Rydbirk, Rasmus, Petukhov, Viktor, Deviatiiarov, Ruslan, Sedmak, Dora, Frank, Erzsebet, Feher, Virginia, Habek, Nikola, Hu, Qiwen, Igolkina, Anna, Roszik, Lilla, Pfisterer, Ulrich, Garcia-Gonzalez, Diego, Petanjek, Zdravko, Adorjan, Istvan, Kharchenko, Peter V., Khodosevich, Konstantin, Batiuk, Mykhailo Y., Tyler, Teadora, Dragicevic, Katarina, Mei, Shenglin, Rydbirk, Rasmus, Petukhov, Viktor, Deviatiiarov, Ruslan, Sedmak, Dora, Frank, Erzsebet, Feher, Virginia, Habek, Nikola, Hu, Qiwen, Igolkina, Anna, Roszik, Lilla, Pfisterer, Ulrich, Garcia-Gonzalez, Diego, Petanjek, Zdravko, Adorjan, Istvan, Kharchenko, Peter V., and Khodosevich, Konstantin

Abstract

Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.

Published
2022

42. 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. Accessory Gene Regulator (agr) Allelic Variants in Cognate Staphylococcus aureus Strain Display Similar Phenotypes

Author

Tan, Li, primary, Huang, Yuyang, additional, Shang, Weilong, additional, Yang, Yi, additional, Peng, Huagang, additional, Hu, Zhen, additional, Wang, Yuting, additional, Rao, Yifan, additional, Hu, Qiwen, additional, Rao, Xiancai, additional, Hu, Xiaomei, additional, Li, Ming, additional, Chen, Kaisen, additional, and Li, Shu, additional

Published
2022
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47. 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

49. Selective vulnerability of supragranular layer neurons in schizophrenia

Author

Batiuk, Mykhailo Y., Tyler, Teadora, Mei, Shenglin, Rydbirk, Rasmus, Petukhov, Viktor, Sedmak, Dora, Frank, Erzsebet, Feher, Virginia, Habek, Nikola, Hu, Qiwen, Igolkina, Anna, Roszik, Lilla, Pfisterer, Ulrich, Petanjek, Zdravko, Adorjan, Istvan, Kharchenko, Peter V., and Khodosevich, Konstantin

Subjects
nervous system
Abstract

Schizophrenia is one of the most wide-spread mental brain disorders with complex and largely unknown etiology. To characterize the impact of schizophrenia at a cellular level, we performed single nucleus RNA sequencing of gt;190,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls (7 vs 11, respectively). In addition, to correlate data with cortical anatomy, gt;100,000 neurons were analyzed topographically by immunohistochemistry in an extended cohort of cases with schizophrenia and controls (10 vs 10). Compositional analysis of RNA sequencing data revealed reduction in relative abundance across all families of GABAergic neurons and a concomitant increase in principal neurons, which was most pronounced for supragranular subtypes (layers 2-3). Moreover, supragranular subtypes of GABAergic interneurons showed most dramatic transcriptomic changes. These results were substantiated by histological analysis, which revealed a reduction in the density of calretinin, calbindin and parvalbumin GABAergic interneurons particularly in layer 2. Common effect of schizophrenia on supragranular neuronal networks was underlined by downregulation of protein processing genes and upregulation of neuronal development/plasticity genes across supragranular subtypes of principal neurons and GABAergic interneurons. In situ hybridization and spatial transcriptomics further confirmed supragranular layer neuron vulnerability, revealing complexity of schizophrenia-affected cortical circuits. These point towards general network impairment within supragranular layers being a core substrate associated with schizophrenia symptomatology.Competing Interest StatementThe authors have declared no competing interest.

Published
2021
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50. Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

Bakken, Trygve E. (author), Jorstad, Nikolas L. (author), Hu, Qiwen (author), Tian, Wei (author), Kalmbach, Brian E. (author), Eggermont, Jeroen (author), Aevermann, Brian D. (author), Höllt, T. (author), Lelieveldt, B.P.F. (author), Bakken, Trygve E. (author), Jorstad, Nikolas L. (author), Hu, Qiwen (author), Tian, Wei (author), Kalmbach, Brian E. (author), Eggermont, Jeroen (author), Aevermann, Brian D. (author), Höllt, T. (author), and Lelieveldt, B.P.F. (author)

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., Author Correction: Comparative cellular analysis of motor cortex in human, marmoset and mouse Download PDF Author Correction Open Access Published: 22 March 2022 Author Correction: Comparative cellular analysis of motor cortex in human, marmoset and mouse Trygve E. Bakken, Nikolas L. Jorstad, …Ed S. Lein Nature (2022)Cite this article 399 Accesses 1 Altmetric Metrics details The Original Article was published on 06 October 2021 Correction to: Nature https://doi-org.tudelft.idm.oclc.org/10.1038/s41586-021-03465-8 Published online 6 October 2021 In the version of this article initially published, the Acknowledgements section was incomplete and has now been amended to include the following: “NIH BRAIN Initiative awards U01 MH121282 to J.R.E and M.M.B, U19 MH114831 to J.R.E. and E.M.C., U19 MH114830 to H.Z., U01 MH114819 to G.F., 1U01MH114828 to K.Z. and J.C., RF1MH123220 to M.H. and R.H.S., and U19 MH114821. NIH awards R01DC019370 to R.H., R24MH114815 to R.H. and O.R.W., and R24 MH114788 to O.R.W. Nancy and Buster Alvord Endowment to C.D.K.” The changes have been made to the HTML and PDF versions of the article, Comp Graphics & Visualisation, Pattern Recognition and Bioinformatics

Published
2021
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