Search

Your search keyword '"Travaglini, Kyle J."' showing total 40 results
Start Over Author "Travaglini, Kyle J."
40 results on '"Travaglini, Kyle J."'

1. Interstitial macrophages are a focus of viral takeover and inflammation in COVID-19 initiation in human lung

Author

Wu, Timothy Ting-Hsuan, Travaglini, Kyle J, Rustagi, Arjun, Xu, Duo, Zhang, Yue, Andronov, Leonid, Jang, SoRi, Gillich, Astrid, Dehghannasiri, Roozbeh, Martínez-Colón, Giovanny J, Beck, Aimee, Liu, Daniel Dan, Wilk, Aaron J, Morri, Maurizio, Trope, Winston L, Bierman, Rob, Weissman, Irving L, Shrager, Joseph B, Quake, Stephen R, Kuo, Christin S, Salzman, Julia, Moerner, WE, Kim, Peter S, Blish, Catherine A, and Krasnow, Mark A

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Lung, Vaccine Related, Emerging Infectious Diseases, Infectious Diseases, Pneumonia, Prevention, Pneumonia & Influenza, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Aetiology, Infection, Respiratory, Good Health and Well Being, Humans, COVID-19, SARS-CoV-2, Macrophages, Inflammation, RNA, Viral, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Early stages of deadly respiratory diseases including COVID-19 are challenging to elucidate in humans. Here, we define cellular tropism and transcriptomic effects of SARS-CoV-2 virus by productively infecting healthy human lung tissue and using scRNA-seq to reconstruct the transcriptional program in "infection pseudotime" for individual lung cell types. SARS-CoV-2 predominantly infected activated interstitial macrophages (IMs), which can accumulate thousands of viral RNA molecules, taking over 60% of the cell transcriptome and forming dense viral RNA bodies while inducing host profibrotic (TGFB1, SPP1) and inflammatory (early interferon response, CCL2/7/8/13, CXCL10, and IL6/10) programs and destroying host cell architecture. Infected alveolar macrophages (AMs) showed none of these extreme responses. Spike-dependent viral entry into AMs used ACE2 and Sialoadhesin/CD169, whereas IM entry used DC-SIGN/CD209. These results identify activated IMs as a prominent site of viral takeover, the focus of inflammation and fibrosis, and suggest targeting CD209 to prevent early pathology in COVID-19 pneumonia. This approach can be generalized to any human lung infection and to evaluate therapeutics.

Published
2024

2. An integrated cell atlas of the lung in health and disease

Author

Sikkema, Lisa, Ramírez-Suástegui, Ciro, Strobl, Daniel C, Gillett, Tessa E, Zappia, Luke, Madissoon, Elo, Markov, Nikolay S, Zaragosi, Laure-Emmanuelle, Ji, Yuge, Ansari, Meshal, Arguel, Marie-Jeanne, Apperloo, Leonie, Banchero, Martin, Bécavin, Christophe, Berg, Marijn, Chichelnitskiy, Evgeny, Chung, Mei-i, Collin, Antoine, Gay, Aurore CA, Gote-Schniering, Janine, Hooshiar Kashani, Baharak, Inecik, Kemal, Jain, Manu, Kapellos, Theodore S, Kole, Tessa M, Leroy, Sylvie, Mayr, Christoph H, Oliver, Amanda J, von Papen, Michael, Peter, Lance, Taylor, Chase J, Walzthoeni, Thomas, Xu, Chuan, Bui, Linh T, De Donno, Carlo, Dony, Leander, Faiz, Alen, Guo, Minzhe, Gutierrez, Austin J, Heumos, Lukas, Huang, Ni, Ibarra, Ignacio L, Jackson, Nathan D, Kadur Lakshminarasimha Murthy, Preetish, Lotfollahi, Mohammad, Tabib, Tracy, Talavera-López, Carlos, Travaglini, Kyle J, Wilbrey-Clark, Anna, Worlock, Kaylee B, Yoshida, Masahiro, van den Berge, Maarten, Bossé, Yohan, Desai, Tushar J, Eickelberg, Oliver, Kaminski, Naftali, Krasnow, Mark A, Lafyatis, Robert, Nikolic, Marko Z, Powell, Joseph E, Rajagopal, Jayaraj, Rojas, Mauricio, Rozenblatt-Rosen, Orit, Seibold, Max A, Sheppard, Dean, Shepherd, Douglas P, Sin, Don D, Timens, Wim, Tsankov, Alexander M, Whitsett, Jeffrey, Xu, Yan, Banovich, Nicholas E, Barbry, Pascal, Duong, Thu Elizabeth, Falk, Christine S, Meyer, Kerstin B, Kropski, Jonathan A, Pe’er, Dana, Schiller, Herbert B, Tata, Purushothama Rao, Schultze, Joachim L, Teichmann, Sara A, Misharin, Alexander V, Nawijn, Martijn C, Luecken, Malte D, and Theis, Fabian J

Subjects
Lung, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Respiratory, Good Health and Well Being, Humans, COVID-19, Pulmonary Fibrosis, Lung Neoplasms, Macrophages, Lung Biological Network Consortium, Medical and Health Sciences, Immunology
Abstract

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.

Published
2023

3. Cell types of origin of the cell-free transcriptome

Author

Jones, Robert C, Karkanias, Jim, Krasnow, Mark, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D’Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Leylek, Rebecca, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Phansalkar, Ragini, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, Vo, Kim Chi, Vorperian, Sevahn K, Wang, Wanxin, Weinstein, Hannah NW, Winkler, Juliane, Wu, Timothy TH, Xie, Jamie, and Yung, Andrea R

Subjects
Human Genome, Genetics, Cell-Free Nucleic Acids, Humans, Transcriptome, Tabula Sapiens Consortium
Abstract

Cell-free RNA from liquid biopsies can be analyzed to determine disease tissue of origin. We extend this concept to identify cell types of origin using the Tabula Sapiens transcriptomic cell atlas as well as individual tissue transcriptomic cell atlases in combination with the Human Protein Atlas RNA consensus dataset. We define cell type signature scores, which allow the inference of cell types that contribute to cell-free RNA for a variety of diseases.

Published
2022

4. The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans

Author

Jones, Robert C, Karkanias, Jim, Krasnow, Mark A, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D'Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea C, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, Vo, Kim Chi, Vorperian, Sevahn K, Wang, Wanxin, Weinstein, Hannah NW, Winkler, Juliane, Wu, Timothy TH, Xie, Jamie, Yung, Andrea R, Zhang, Yue, and Detweiler, Angela M

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Generic health relevance, Atlases as Topic, B-Lymphocytes, Cells, Humans, Organ Specificity, RNA Splicing, Single-Cell Analysis, T-Lymphocytes, Transcriptome, Tabula Sapiens Consortium*, General Science & Technology
Abstract

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Published
2022

6. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris

Author

Schaum, Nicholas, Karkanias, Jim, Neff, Norma F, May, Andrew P, Quake, Stephen R, Wyss-Coray, Tony, Darmanis, Spyros, Batson, Joshua, Botvinnik, Olga, Chen, Michelle B, Chen, Steven, Green, Foad, Jones, Robert C, Maynard, Ashley, Penland, Lolita, Pisco, Angela Oliveira, Sit, Rene V, Stanley, Geoffrey M, Webber, James T, Zanini, Fabio, Baghel, Ankit S, Bakerman, Isaac, Bansal, Ishita, Berdnik, Daniela, Bilen, Biter, Brownfield, Douglas, Cain, Corey, Cho, Min, Cirolia, Giana, Conley, Stephanie D, Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Dulgeroff, Laughing Bear Torrez, Ebadi, Hamid, Espinoza, F Hernan, Fish, Matt, Gan, Qiang, George, Benson M, Gillich, Astrid, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S, Hang, Yan, Hosseinzadeh, Shayan, Huang, Albin, Iram, Tal, Isobe, Taichi, Ives, Feather, Kao, Kevin S, Karnam, Guruswamy, Kershner, Aaron M, Kiss, Bernhard M, Kong, William, Kumar, Maya E, Lam, Jonathan Y, Lee, Davis P, Lee, Song E, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Manjunath, Anoop, May, Kaia L, May, Oliver L, McKay, Marina, Metzger, Ross J, Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N, Ng, Katharine M, Noh, Joseph, Patkar, Rasika, Peng, Weng Chuan, Puccinelli, Robert, Sikandar, Shaheen S, Sinha, Rahul, Szade, Krzysztof, Tan, Weilun, Tato, Cristina, Tellez, Krissie, Travaglini, Kyle J, Tropini, Carolina, Waldburger, Lucas, van Weele, Linda J, Wosczyna, Michael N, Xiang, Jinyi, Xue, Soso, Youngyunpipatkul, Justin, Zardeneta, Macy E, Zhang, Fan, Zhou, Lu, Castro, Paola, Croote, Derek, DeRisi, Joseph L, Kuo, Christin S, and Lehallier, Benoit

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, 1.5 Resources and infrastructure (underpinning), Generic health relevance, Animals, Cell Biology, Endothelial Cells, Female, Flow Cytometry, Gene Expression Profiling, Male, Mice, Mice, Inbred C57BL, Microfluidics, Organ Specificity, Single-Cell Analysis, T-Lymphocytes, Transcription Factors, Transcriptome, Tabula Muris Consortium, Overall coordination, Logistical coordination, Organ collection and processing, Library preparation and sequencing, Computational data analysis, Cell type annotation, Writing group, Supplemental text writing group, Principal investigators, General Science & Technology
Abstract

Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. The cumulative data provide the foundation for an atlas of transcriptomic cell biology.

Published
2018

7. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Author

Muus, Christoph, Luecken, Malte D., Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit Dhaval, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik A., Duong, Elizabeth Thu, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam L., Chung, Hattie, Montoro, Daniel T., Adams, Taylor, Aliee, Hananeh, Allon, Samuel J., Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh T., Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas M., Cuoco, Michael S., Cuomo, Anna S. E., Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David S., Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin J., Habermann, Arun C., Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros S., Kuo, Christin S., Larsson, Ludvig, Leney-Greene, Michael A., Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif S., Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph H., Mbano, Ian M., McAdams, Alexi M., Nabhan, Ahmad N., Nyquist, Sarah K., Penland, Lolita, Poirion, Olivier B., Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas C., Shea, Conor V., Shi, Xingyi, Sinha, Rahul, Sit, Rene V., Slowikowski, Kamil, Slyper, Michal, Smith, Neal P., Sountoulidis, Alex, Strunz, Maximilian, Sullivan, Travis B., Sun, Dawei, Talavera-López, Carlos, Tan, Peng, Tantivit, Jessica, Travaglini, Kyle J., Tucker, Nathan R., Vernon, Katherine A., Wadsworth, Marc H., Waldman, Julia, Wang, Xiuting, Xu, Ke, Yan, Wenjun, Zhao, William, and Ziegler, Carly G. K.

Published
2021
Full Text
View/download PDF

8. A molecular cell atlas of the human lung from single-cell RNA sequencing

Author

Travaglini, Kyle J., Nabhan, Ahmad N., Penland, Lolita, Sinha, Rahul, Gillich, Astrid, Sit, Rene V., and Chang, Stephen

Subjects
RNA sequencing -- Methods, Molecular biology -- Analysis, Lungs -- Physiological aspects, Cells -- Identification and classification, Atlases -- Usage, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles.sup.1-9, it has been difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, we create an extensive cell atlas of the human lung. We define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 out of 45 previously known cell types and 14 previously unknown ones. This comprehensive molecular atlas identifies the biochemical functions of lung cells and the transcription factors and markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signalling interactions and immune cell homing; and identifies cell types that are directly affected by lung disease genes and respiratory viruses. By comparing human and mouse data, we identified 17 molecular cell types that have been gained or lost during lung evolution and others with substantially altered expression profiles, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions and interactions are achieved in development and tissue engineering and altered in disease and evolution. Expression profiling on 75,000 single cells creates a comprehensive cell atlas of the human lung that includes 41 out of 45 previously known cell types and 14 new ones., Author(s): Kyle J. Travaglini [sup.1] [sup.2] , Ahmad N. Nabhan [sup.1] [sup.2] [sup.12] , Lolita Penland [sup.3] [sup.13] , Rahul Sinha [sup.4] [sup.5] , Astrid Gillich [sup.1] [sup.2] , Rene [...]

Published
2020
Full Text
View/download PDF

9. Molecular hallmarks of Alzheimer’s disease with a multimodal single cell atlas of the cortex

Author

Travaglini, Kyle J, primary, Gabitto, Mariano I, additional, Ariza, Jeanelle, additional, Ding, Yi, additional, Mahoney, Joseph T, additional, Casper, Tamara, additional, Chakrabarty, Rushil, additional, Clark, Michael, additional, Crane, Paul K, additional, Dee, Nick, additional, Ferrer, Rebecca, additional, Gatto, Nicole M, additional, Gloe, Jessica, additional, Goldy, Jeff, additional, Grabowski, Thomas J, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Hawrylycz, Michael J, additional, Hodge, Rebecca D, additional, Jayadev, Suman, additional, Kaplan, Eitan S, additional, Keene, C Dirk, additional, Larson, Eric B, additional, Latimer, Caitlin S, additional, Levi, Boaz P, additional, Melief, Erica J, additional, Meyerdierks, Emma, additional, Mukherjee, Shubhabrata, additional, Pham, Thanh, additional, Rachleff, Victoria M, additional, Smith, Kimberly, additional, Torkelson, Amy, additional, Lein, Ed S, additional, and Miller, Jeremy A, additional

Published
2023
Full Text
View/download PDF

10. Multimodal and multiregional atlas of Alzheimer’s disease changes

Author

Gabitto, Mariano I, primary, Travaglini, Kyle J, additional, Ariza, Jeanelle, additional, Close, Jennie, additional, Ding, Yi, additional, Long, Brian, additional, Rachleff, Victoria M, additional, Chakrabarty, Rushil, additional, Crane, Paul K, additional, Ferrer, Rebecca, additional, Gatto, Nicole M, additional, Goldy, Jeff, additional, Grabowski, Thomas J, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Hawrylycz, Michael J, additional, Hodge, Rebecca D, additional, Jayadev, Suman, additional, Kaplan, Eitan S, additional, Keene, C Dirk, additional, Larson, Eric B, additional, Latimer, Caitlin S, additional, Levi, Boaz P, additional, Mahoney, Joseph T, additional, Melief, Erica J, additional, Miller, Jeremy A, additional, Mukherjee, Shubhabrata, additional, Pham, Thanh, additional, Smith, Kimberly, additional, Torkelson, Amy, additional, Chakka, Anish Bhaswanth, additional, and Lein, Ed S, additional

Published
2023
Full Text
View/download PDF

11. Capillary cell-type specialization in the alveolus

Author

Gillich, Astrid, Zhang, Fan, Farmer, Colleen G., Travaglini, Kyle J., Tan, Serena Y., Gu, Mingxia, and Zhou, Bin

Subjects
Cell physiology -- Analysis, Stem cells -- Identification and classification, Capillaries -- Analysis, Pulmonary alveoli -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood.sup.1. Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex 'Swiss-cheese'-like morphologies and distinct functions. The first cell type, which we term the 'aerocyte', is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap ('general' capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air-blood barrier and gas exchange in health, disease and evolution. Single-cell analysis of blood vessels in the alveolus, the site of chronic disease and virus-induced lung injury, reveals two intermingled endothelial cell types with specialized gas exchange and stem cell functions., Author(s): Astrid Gillich [sup.1] [sup.2] [sup.3] , Fan Zhang [sup.3] , Colleen G. Farmer [sup.4] , Kyle J. Travaglini [sup.1] [sup.2] [sup.3] , Serena Y. Tan [sup.5] , Mingxia Gu [...]

Published
2020
Full Text
View/download PDF

12. Translational roles of elongation factor 2 protein lysine methylation.

Author

Dzialo, Maria C, Travaglini, Kyle J, Shen, Sean, Roy, Kevin, Chanfreau, Guillaume F, Loo, Joseph A, and Clarke, Steven G

Subjects
Saccharomyces cerevisiae, Peptide Elongation Factor 2, Methyltransferases, Saccharomyces cerevisiae Proteins, Phylogeny, Protein Biosynthesis, Protein Processing, Post-Translational, Amino Acid Sequence, Catalytic Domain, Conserved Sequence, Methylation, Models, Molecular, Molecular Sequence Data, Lysine Methylation, Protein Methylation, Protein Synthesis, Ribosome Function, S-Adenosylmethionine, Translation Elongation Factor, Genetics, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biochemistry & Molecular Biology
Abstract

Methylation of various components of the translational machinery has been shown to globally affect protein synthesis. Little is currently known about the role of lysine methylation on elongation factors. Here we show that in Saccharomyces cerevisiae, the product of the EFM3/YJR129C gene is responsible for the trimethylation of lysine 509 on elongation factor 2. Deletion of EFM3 or of the previously described EFM2 increases sensitivity to antibiotics that target translation and decreases translational fidelity. Furthermore, the amino acid sequences of Efm3 and Efm2, as well as their respective methylation sites on EF2, are conserved in other eukaryotes. These results suggest the importance of lysine methylation modification of EF2 in fine tuning the translational apparatus.

Published
2014

13. 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
Full Text
View/download PDF

14. 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
Full Text
View/download PDF

15. Molecular hallmarks of heterochronic parabiosis at single-cell resolution

Author

Pálovics, Róbert, Keller, Andreas, Schaum, Nicholas, Tan, Weilun, Fehlmann, Tobias, Borja, Michael, Kern, Fabian, Bonanno, Liana, Calcuttawala, Kruti, Webber, James, McGeever, Aaron, Almanzar, Nicole, Antony, Jane, Baghel, Ankit S., Bakerman, Isaac, Bansal, Ishita, Barres, Ben A., Beachy, Philip A., Berdnik, Daniela, Bilen, Biter, Brownfield, Douglas, Cain, Corey, Chan, Charles K. F., Chen, Michelle B., Clarke, Michael F., Conley, Stephanie D., Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Ebadi, Hamid, Espinoza, F. Hernán, Fish, Matt, Gan, Qiang, George, Benson M., Gillich, Astrid, Gòmez-Sjöberg, Rafael, Green, Foad, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S., Hahn, Oliver, Haney, Michael Seamus, Hang, Yan, Harris, Lincoln, He, Mu, Hosseinzadeh, Shayan, Huang, Albin, Huang, Kerwyn Casey, Iram, Tal, Isobe, Taichi, Ives, Feather, Jones, Robert C., Kao, Kevin S., Karnam, Guruswamy, Kershner, Aaron M., Khoury, Nathalie, Kim, Seung K., Kiss, Bernhard M., Kong, William, Krasnow, Mark A., Kumar, Maya E., Kuo, Christin S., Lam, Jonathan, Lee, Davis P., Lee, Song E., Lehallier, Benoit, Leventhal, Olivia, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Lugo-Fagundo, Maria F., Manjunath, Anoop, May, Andrew P., Maynard, Ashley, McKay, Marina, McNerney, M. Windy, Merrill, Bryan, Metzger, Ross J., Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N., Ng, Katharine M., Nguyen, Patricia K., Noh, Joseph, Nusse, Roel, Patkar, Rasika, Peng, Weng Chuan, Penland, Lolita, Pollard, Katherine, Puccinelli, Robert, Qi, Zhen, Rando, Thomas A., Rulifson, Eric J., Segal, Joe M., Sikandar, Shaheen S., Sinha, Rahul, Sit, Rene V., Sonnenburg, Justin, Staehli, Daniel, Szade, Krzysztof, Tan, Michelle, Tato, Cristina, Tellez, Krissie, Torrez Dulgeroff, Laughing Bear, Travaglini, Kyle J., Tropini, Carolina, Tsui, Margaret, Waldburger, Lucas, Wang, Bruce M., van Weele, Linda J., Weinberg, Kenneth, Weissman, Irving L., Wosczyna, Michael N., Wu, Sean M., Xiang, Jinyi, Xue, Soso, Yamauchi, Kevin A., Yang, Andrew C., Yerra, Lakshmi P., Youngyunpipatkul, Justin, Yu, Brian, Zanini, Fabio, Zardeneta, Macy E., Zee, Alexander, Zhao, Chunyu, Zhang, Fan, Zhang, Hui, Zhang, Martin Jinye, Zhou, Lu, Zou, James, Luo, Jian, Pisco, Angela Oliveira, Karkanias, Jim, Neff, Norma F., Darmanis, Spyros, Quake, Stephen R., and Wyss-Coray, Tony

Subjects
Aging, Multidisciplinary, Parabiosis, Mesenchymal Stem Cells, Hematopoietic Stem Cells, Article, Organ Specificity/genetics, Mitochondria, Electron Transport, Electron Transport/genetics, Organ Specificity, Aging/genetics, Adipocytes, Hepatocytes, Rejuvenation, RNA-Seq, Single-Cell Analysis
Abstract

The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.

Published
2022

16. A multimodal atlas of the molecular and cellular changes to cortex driven by Alzheimer’s disease

Author

Travaglini, Kyle J, primary, Gabitto, Mariano, additional, Ding, Yi, additional, Ariza, Jeanelle, additional, Chakrabarty, Rushil, additional, Crane, Paul K., additional, Ferrer, Rebecca, additional, Goldy, Jeff, additional, Grabowski, Thomas J, additional, Guilford, Nathan, additional, Guzman, Junitta, additional, Hawrylycz, Michael J, additional, Hodge, Rebecca D, additional, Jayadev, Suman, additional, Kaplan, Eitan S, additional, Keene, C Dirk, additional, Larson, Eric B, additional, Latimer, Caitlin S, additional, Levi, Boaz, additional, Mahoney, Joseph, additional, Melief, Erica J, additional, Mukherjee, Shubhabrata, additional, Pham, Thanh, additional, Rachleff, Victoria M, additional, Smith, Kimberly A, additional, Torkelson, Amy, additional, Lein, Ed S, additional, and Miller, Jeremy A, additional

Published
2022
Full Text
View/download PDF

17. 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
Full Text
View/download PDF

18. Inter-individual variation in human cortical cell type abundance and expression

Author

Johansen, Nelson, primary, Somasundaram, Saroja, additional, Travaglini, Kyle J., additional, Yanny, Anna Marie, additional, Shumyatcher, Maya, additional, Casper, Tamara, additional, Cobbs, Charles, additional, Dee, Nick, additional, Ellenbogen, Richard, additional, Ferreira, Manuel, additional, Goldy, Jeff, additional, Guzman, Junitta, additional, Gwinn, Ryder, additional, Hirschstein, Daniel, additional, Jorstad, Nikolas L., additional, Keene, C. Dirk, additional, Ko, Andrew, additional, Levi, Boaz P., additional, Ojemann, Jeffrey G., additional, Pham, Thanh, additional, Shapovalova, Nadiya, additional, Silbergeld, Daniel, additional, Sulc, Josef, additional, Torkelson, Amy, additional, Tung, Herman, additional, Smith, Kimberly, additional, Lein, Ed S., additional, Bakken, Trygve E., additional, Hodge, Rebecca D., additional, and Miller, Jeremy A., additional

Published
2022
Full Text
View/download PDF

19. 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
Full Text
View/download PDF

20. The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans

Author

Tabula Sapiens Consortium, Jones, Robert C, Karkanias, Jim, Krasnow, Mark A, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D'Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Leylek, Rebecca, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Phansalkar, Ragini, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea C, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, and Vo, Kim Chi

Subjects
B-Lymphocytes, General Science & Technology, Cells, T-Lymphocytes, RNA Splicing, Human Genome, Tabula Sapiens Consortium, Atlases as Topic, Organ Specificity, Genetics, Humans, Generic health relevance, Single-Cell Analysis, Transcriptome, Biotechnology
Abstract

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Published
2022

21. Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung

Author

Wu, Timothy Ting-Hsuan, primary, Travaglini, Kyle J., additional, Rustagi, Arjun, additional, Xu, Duo, additional, Zhang, Yue, additional, Jang, SoRi K., additional, Gillich, Astrid, additional, Dehghannasiri, Roozbeh, additional, Martinez-Colon, Giovanny, additional, Beck, Aimee, additional, Wilk, Aaron J., additional, Morri, Maurizio, additional, Trope, Winston L., additional, Shrager, Joseph B., additional, Quake, Stephen R., additional, Kuo, Christin S., additional, Salzman, Julia, additional, Kim, Peter S., additional, Blish, Catherine A., additional, and Krasnow, Mark A., additional

Published
2022
Full Text
View/download PDF

22. Dissecting alveolar patterning and maintenance at single‐cell resolution

Author

Gillich, Astrid, primary, Brownfield, Douglas G., additional, Travaglini, Kyle J., additional, Zhang, Fan, additional, Farmer, Colleen G., additional, St. Julien, Krystal R., additional, Tan, Serena Y., additional, Gu, Mingxia, additional, Zhou, Bin, additional, Feinstein, Jeffrey A., additional, Metzger, Ross J., additional, and Krasnow, Mark A., additional

Published
2022
Full Text
View/download PDF

23. The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans.

Author

Tabula Sapiens Consortium*, Tabula Sapiens Consortium*, Jones, Robert C, Karkanias, Jim, Krasnow, Mark A, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D'Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Leylek, Rebecca, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Phansalkar, Ragini, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea C, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, Vo, Kim Chi, Tabula Sapiens Consortium*, Tabula Sapiens Consortium*, Jones, Robert C, Karkanias, Jim, Krasnow, Mark A, Pisco, Angela Oliveira, Quake, Stephen R, Salzman, Julia, Yosef, Nir, Bulthaup, Bryan, Brown, Phillip, Harper, William, Hemenez, Marisa, Ponnusamy, Ravikumar, Salehi, Ahmad, Sanagavarapu, Bhavani A, Spallino, Eileen, Aaron, Ksenia A, Concepcion, Waldo, Gardner, James M, Kelly, Burnett, Neidlinger, Nikole, Wang, Zifa, Crasta, Sheela, Kolluru, Saroja, Morri, Maurizio, Tan, Serena Y, Travaglini, Kyle J, Xu, Chenling, Alcántara-Hernández, Marcela, Almanzar, Nicole, Antony, Jane, Beyersdorf, Benjamin, Burhan, Deviana, Calcuttawala, Kruti, Carter, Matthew M, Chan, Charles KF, Chang, Charles A, Chang, Stephen, Colville, Alex, Culver, Rebecca N, Cvijović, Ivana, D'Amato, Gaetano, Ezran, Camille, Galdos, Francisco X, Gillich, Astrid, Goodyer, William R, Hang, Yan, Hayashi, Alyssa, Houshdaran, Sahar, Huang, Xianxi, Irwin, Juan C, Jang, SoRi, Juanico, Julia Vallve, Kershner, Aaron M, Kim, Soochi, Kiss, Bernhard, Kong, William, Kumar, Maya E, Kuo, Angera H, Leylek, Rebecca, Li, Baoxiang, Loeb, Gabriel B, Lu, Wan-Jin, Mantri, Sruthi, Markovic, Maxim, McAlpine, Patrick L, de Morree, Antoine, Mrouj, Karim, Mukherjee, Shravani, Muser, Tyler, Neuhöfer, Patrick, Nguyen, Thi D, Perez, Kimberly, Phansalkar, Ragini, Puluca, Nazan, Qi, Zhen, Rao, Poorvi, Raquer-McKay, Hayley, Schaum, Nicholas, Scott, Bronwyn, Seddighzadeh, Bobak, Segal, Joe, Sen, Sushmita, Sikandar, Shaheen, Spencer, Sean P, Steffes, Lea C, Subramaniam, Varun R, Swarup, Aditi, Swift, Michael, Van Treuren, Will, Trimm, Emily, Veizades, Stefan, Vijayakumar, Sivakamasundari, and Vo, Kim Chi

Abstract

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual.

Published
2022

25. Ageing hallmarks exhibit organ-specific temporal signatures

Author

Schaum, Nicholas, Lehallier, Benoit, Hahn, Oliver, Pálovics, Róbert, Hosseinzadeh, Shayan, Lee, Song E., Sit, Rene, Lee, Davis P., Losada, Patricia Morán, Zardeneta, Macy E., Fehlmann, Tobias, Webber, James T., McGeever, Aaron, Calcuttawala, Kruti, Zhang, Hui, Berdnik, Daniela, Mathur, Vidhu, Tan, Weilun, Zee, Alexander, Tan, Michelle, Almanzar, Nicole, Antony, Jane, Baghel, Ankit S., Bakerman, Isaac, Bansal, Ishita, Barres, Ben A., Beachy, Philip A., Bilen, Biter, Brownfield, Douglas, Cain, Corey, Chan, Charles K. F., Chen, Michelle B., Clarke, Michael F., Conley, Stephanie D., Darmanis, Spyros, Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Ebadi, Hamid, Espinoza, F. Hernán, Fish, Matt, Gan, Qiang, George, Benson M., Gillich, Astrid, Gòmez-Sjöberg, Rafael, Green, Foad, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S., Haney, Michael Seamus, Hang, Yan, Harris, Lincoln, He, Mu, Huang, Albin, Huang, Kerwyn Casey, Iram, Tal, Isobe, Taichi, Ives, Feather, Jones, Robert, Kao, Kevin S., Karkanias, Jim, Karnam, Guruswamy, Keller, Andreas, Kershner, Aaron M., Khoury, Nathalie, Kim, Seung K., Kiss, Bernhard M., Kong, William, Krasnow, Mark A., Kumar, Maya E., Kuo, Christin S., Lam, Jonathan Y., Leventhal, Olivia, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Lugo-Fagundo, Maria F., Manjunath, Anoop, May, Andrew P., Maynard, Ashley, McKay, Marina, McNerney, M. Windy, Merrill, Bryan, Metzger, Ross J., Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N., Neff, Norma F., Ng, Katharine M., Nguyen, Patricia K., Noh, Joseph, Nusse, Roel, Patkar, Rasika, Peng, Weng Chuan, Penland, Lolita, Pisco, Angela Oliveira, Pollard, Katherine, Puccinelli, Robert, Qi, Zhen, Quake, Stephen R., Rando, Thomas A., Rulifson, Eric J., Segal, Joe M., Sikandar, Shaheen S., Sinha, Rahul, Sonnenburg, Justin, Staehli, Daniel, Szade, Krzysztof, Tato, Cristina, Tellez, Krissie, Torrez Dulgeroff, Laughing Bear, Travaglini, Kyle J., Tropini, Carolina, Tsui, Margaret, Waldburger, Lucas, Wang, Bruce M., van Weele, Linda J., Weinberg, Kenneth, Weissman, Irving L., Wosczyna, Michael N., Wu, Sean M., Wyss-Coray, Tony, Xiang, Jinyi, Xue, Soso, Yamauchi, Kevin A., Yang, Andrew C., Yerra, Lakshmi P., Youngyunpipatkul, Justin, Yu, Brian, Zanini, Fabio, Zhao, Chunyu, Zhang, Fan, Zhang, Martin Jinye, Zhou, Lu, and Zou, James

Subjects
0301 basic medicine, Male, Aging, Time Factors, T-Lymphocytes, Plasma Cells, RNA-Seq, Biology, Article, Transcriptome, 03 medical and health sciences, Mice, 0302 clinical medicine, Gene expression, Animals, RNA, Messenger, Gene, Regulation of gene expression, Multidisciplinary, Blood Proteins, Cell biology, 030104 developmental biology, Proteostasis, Gene Expression Regulation, Ageing, Organ Specificity, Immunoglobulin J-Chains, Unfolded protein binding, Female, Single-Cell Analysis, 030217 neurology & neurosurgery
Abstract

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1—these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2—or ‘Mouse Ageing Cell Atlas’—which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions—including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue—including plasma cells that express immunoglobulin J—which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age. Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

Published
2020

26. Rate of memory decline is associated with neuronal nuclear protein (NeuN) positive cells count in middle temporal gyrus in the Adult Changes in Thought (ACT) autopsy cohort.

Author

Mukherjee, Shubhabrata, Ariza, Jeanelle, Gibbons, Laura E, Rachleff, Victoria M, Travaglini, Kyle J, Latimer, Caitlin S, Melief, Erica J, Campos, John S, Gabitto, Mariano, Miller, Jeremy A, Ding, Yi, Levi, Boaz, Long, Brian, Kaplan, Eitan S, Hodge, Rebecca D, Larson, Eric B, Crane, Paul K., Lein, Ed S, and Keene, C. Dirk

Abstract

Background: The trace of memory has not been well studied in middle temporal gyrus (MTG). Although neuronal loss is minimal in most cortical regions of the aging brain, changes in synaptic physiology of ageing neurons may contribute to altered connectivity. In the Adult Changes in Thought (ACT) autopsy cohort, we explored if memory decline is associated with NeuN (neuronal nuclear protein), a biomarker for mature neurons, in MTG. Method: ACT study participants were 5,763 older adults randomly sampled from an integrated healthcare delivery system in King County, Washington. We standardized composite memory scores to N(0,1) at baseline. We calculated slopes of memory decline over time using mixed‐effects models, where time was parameterized as years before death. Among 69 individuals who underwent brain autopsy, we measured NeuN positive cell count from whole slide image analysis using HALO in five tissue layers (molecular, external granular, external pyramidal, internal granular, internal pyramidal + multiform) from brain tissue in MTG. In each layer, we normalized NeuN positive cell count over the tissue area. We derived an average NeuN positive cell count (ANPCC) by averaging the values across the layers (Figure 1). We regressed ANPCC on memory slope, adjusting for age at death and sex. In secondary models, we added disease severity (Braak staging) and presence of APOE ε4 alleles separately. We also analyzed layer‐specific ANPCC. Result: 64 individuals were included for analysis (Table 1). Memory decline in this sample was 0.10 units per year, similar to the entire cohort. Slower decline in memory (β = 0.10; p‐value = 0.002) was significantly associated with increased average ANPCC (Table 2). Adjusting for Braak staging and APOE ε4 gave similar results. Findings were statistically significant across all but the molecular layer. Conclusion: ANPCC is associated with slower memory decline in multiple neocortical layers in MTG, irrespective of disease staging or APOE genotype. Since Alzheimer's disease afflicts adult neuronal populations, survival mechanisms in mature neurons are likely to be either reversed or circumvented during neurodegeneration. Further analyses are needed to understand the functional range of NeuN and processes that lead to loss of NeuN immunoreactivity in cells. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

27. Profile of an unknown airway cell

Author

Travaglini, Kyle J. and Krasnow, Mark A.

Subjects
Cystic fibrosis -- Genetic aspects, Cells (Biology) -- Identification and classification -- Health aspects, RNA sequencing -- Methods, Trachea -- Physiological aspects, Microscopy, Scientists, Genes, Electron microscopy, RNA, Physicians, Fibrosis, Microorganisms, Biochemistry, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

RNA sequencing of single cells in the mammalian trachea reveals a previously unknown airway cell that expresses genes involved in fluid and solute balance, and that might play a part in cystic fibrosis.RNA sequencing of single cells in the mammalian trachea reveals a previously unknown airway cell that expresses genes involved in fluid and solute balance, and that might play a part in cystic fibrosis., Author(s): Kyle J. Travaglini, Mark A. KrasnowAuthor Affiliations:Profile of an unknown airway cell Over the past two centuries, light and electron microscopy have enabled scientists to identify six or more [...]

Published
2018
Full Text
View/download PDF

28. A molecular cell atlas of the human lung from single cell RNA sequencing

Author

Travaglini, Kyle J., primary, Nabhan, Ahmad N., additional, Penland, Lolita, additional, Sinha, Rahul, additional, Gillich, Astrid, additional, Sit, Rene V., additional, Chang, Stephen, additional, Conley, Stephanie D., additional, Mori, Yasuo, additional, Seita, Jun, additional, Berry, Gerald J., additional, Shrager, Joseph B., additional, Metzger, Ross J., additional, Kuo, Christin S., additional, Neff, Norma, additional, Weissman, Irving L., additional, Quake, Stephen R., additional, and Krasnow, Mark A., additional

Published
2019
Full Text
View/download PDF

29. Single-cell transcriptomic characterization of 20 organs and tissues from individual mice creates a Tabula Muris

Author

Schaum, Nicholas, primary, Karkanias, Jim, additional, Neff, Norma F, additional, May, Andrew P., additional, Quake, Stephen R., additional, Wyss-Coray, Tony, additional, Darmanis, Spyros, additional, Batson, Joshua, additional, Botvinnik, Olga, additional, Chen, Michelle B., additional, Chen, Steven, additional, Green, Foad, additional, Jones, Robert, additional, Maynard, Ashley, additional, Penland, Lolita, additional, Sit, Rene V., additional, Stanley, Geoffrey M., additional, Webber, James T., additional, Zanini, Fabio, additional, Baghel, Ankit S., additional, Bakerman, Isaac, additional, Bansal, Ishita, additional, Berdnik, Daniela, additional, Bilen, Biter, additional, Brownfield, Douglas, additional, Cain, Corey, additional, Cho, Min, additional, Cirolia, Giana, additional, Conley, Stephanie D., additional, Demers, Aaron, additional, Demir, Kubilay, additional, Morree, Antoine de, additional, Divita, Tessa, additional, Bois, Haley du, additional, Dulgeroff, Laughing Bear Torrez, additional, Ebadi, Hamid, additional, Espinoza, F. Hernan, additional, Fish, Matt, additional, Gan, Qiang, additional, George, Benson M., additional, Gillich, Astrid, additional, Genetiano, Geraldine, additional, Gu, Xueying, additional, Gulati, Gunsagar S., additional, Hang, Yan, additional, Hosseinzadeh, Shayan, additional, Huang, Albin, additional, Iram, Tal, additional, Isobe, Taichi, additional, Ives, Feather, additional, Kao, Kevin S., additional, Karnam, Guruswamy, additional, Kershner, Aaron M., additional, Kiss, Bernhard, additional, Kong, William, additional, Kumar, Maya E., additional, Lam, Jonathan, additional, Lee, Davis P., additional, Lee, Song E., additional, Li, Guang, additional, Li, Qingyun, additional, Liu, Ling, additional, Lo, Annie, additional, Lu, Wan-Jin, additional, Manjunath, Anoop, additional, May, Kaia L., additional, May, Oliver L., additional, McKay, Marina, additional, Metzger, Ross J., additional, Mignardi, Marco, additional, Min, Dullei, additional, Nabhan, Ahmad N., additional, Ng, Katharine M., additional, Noh, Joseph, additional, Patkar, Rasika, additional, Peng, Weng Chuan, additional, Puccinelli, Robert, additional, Rulifson, Eric J., additional, Schaum, Nicholas, additional, Sikandar, Shaheen S., additional, Sinha, Rahul, additional, Sit, Rene V, additional, Szade, Krzysztof, additional, Tan, Weilun, additional, Tato, Cristina, additional, Tellez, Krissie, additional, Travaglini, Kyle J., additional, Tropini, Carolina, additional, Waldburger, Lucas, additional, Weele, Linda J. van, additional, Wosczyna, Michael N., additional, Xiang, Jinyi, additional, Xue, Soso, additional, Youngyunpipatkul, Justin, additional, Zardeneta, Macy E., additional, Zhang, Fan, additional, Zhou, Lu, additional, Neff, Norma F., additional, Castro, Paola, additional, Croote, Derek, additional, DeRisi, Joseph L., additional, Pisco, Angela, additional, Kiss, Bernhard M., additional, Kuo, Christin S., additional, Lehallier, Benoit, additional, Nguyen, Patricia K., additional, Tan, Serena Y., additional, Wang, Bruce M., additional, Yousef, Hanadie, additional, Beachy, Philip A., additional, Chan, Charles K. F., additional, Huang, Kerwyn Casey, additional, Weinberg, Kenneth, additional, Wu, Sean, additional, Barres, Ben A., additional, Clarke, Michael F., additional, Kim, Seung K., additional, Krasnow, Mark A., additional, Neff, Norma, additional, Nusse, Roel, additional, Rando, Thomas A., additional, Sonnenburg, Justin, additional, Weissman, Irving L., additional, and Wu, Sean M., additional

Published
2017
Full Text
View/download PDF

30. Index switching causes “spreading-of-signal” among multiplexed samples in Illumina HiSeq 4000 DNA sequencing

Author

Sinha, Rahul, primary, Stanley, Geoff, additional, Gulati, Gunsagar S., additional, Ezran, Camille, additional, Travaglini, Kyle J., additional, Wei, Eric, additional, Chan, Charles K.F., additional, Nabhan, Ahmad N., additional, Su, Tianying, additional, Morganti, Rachel M., additional, Conley, Stephanie D., additional, Chaib, Hassan, additional, Red-Horse, Kristy, additional, Longaker, Michael T., additional, Snyder, Michael P., additional, Krasnow, Mark A., additional, and Weissman, Irving L., additional

Published
2017
Full Text
View/download PDF

31. Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

Author

Lebensohn, Andres M, primary, Dubey, Ramin, additional, Neitzel, Leif R, additional, Tacchelly-Benites, Ofelia, additional, Yang, Eungi, additional, Marceau, Caleb D, additional, Davis, Eric M, additional, Patel, Bhaven B, additional, Bahrami-Nejad, Zahra, additional, Travaglini, Kyle J, additional, Ahmed, Yashi, additional, Lee, Ethan, additional, Carette, Jan E, additional, and Rohatgi, Rajat, additional

Published
2016
Full Text
View/download PDF

32. Author response: Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

Author

Lebensohn, Andres M, primary, Dubey, Ramin, additional, Neitzel, Leif R, additional, Tacchelly-Benites, Ofelia, additional, Yang, Eungi, additional, Marceau, Caleb D, additional, Davis, Eric M, additional, Patel, Bhaven B, additional, Bahrami-Nejad, Zahra, additional, Travaglini, Kyle J, additional, Ahmed, Yashi, additional, Lee, Ethan, additional, Carette, Jan E, additional, and Rohatgi, Rajat, additional

Published
2016
Full Text
View/download PDF

33. Comparative transcriptomics reveals human-specific cortical features.

Author

Jorstad, Nikolas L., Song, Janet H. T., Exposito-Alonso, David, Suresh, Hamsini, Castro-Pacheco, Nathan, Krienen, Fenna M., Yanny, Anna Marie, Close, Jennie, Gelfand, Emily, Long, Brian, Seeman, Stephanie C., Travaglini, Kyle J., Basu, Soumyadeep, Beaudin, Marc, Bertagnolli, Darren, Crow, Megan, Song-Lin Ding, Eggermont, Jeroen, Glandon, Alexandra, and Goldy, Jeff

Published
2023
Full Text
View/download PDF

34. Interindividual variation in human cortical cell type abundance and expression.

Author

Johansen, Nelson, Somasundaram, Saroja, Travaglini, Kyle J., Yanny, Anna Marie, Shumyatcher, Maya, Casper, Tamara, Cobbs, Charles, Dee, Nick, Ellenbogen, Richard, Ferreira, Manuel, Goldy, Jeff, Guzman, Junitta, Gwinn, Ryder, Hirschstein, Daniel, Jorstad, Nikolas L., Keene, C. Dirk, Ko, Andrew, Levi, Boaz P., Ojemann, Jeffrey G., and ThanhPham

Published
2023
Full Text
View/download PDF

37. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Author

Christoph, Muus, Luecken , Malte D., Gökcen, Eraslan, Lisa, Sikkema, Avinash, Waghray, Graham, Heimberg, Yoshihiko, Kobayashi, Eeshit Dhaval Vaishnav, Ayshwarya, Subramanian, Christopher, Smillie, Jagadeesh, Karthik A., Elizabeth Thu Duong, Evgenij, Fiskin, Elena Torlai Triglia, Meshal, Ansari, Peiwen, Cai, Brian, Lin, Justin, Buchanan, Sijia, Chen, Jian, Shu, Haber, Adam L., Hattie, Chung, Montoro, Daniel T., Taylor, Adams, Hananeh, Aliee, Allon, Samuel J., Zaneta, Andrusivova, Ilias, Angelidis, Orr, Ashenberg, Kevin, Bassler, Christophe, Bécavin, Inbal, Benhar, Joseph, Bergenstråhle, Ludvig, Bergenstråhle, Liam, Bolt, Emelie, Braun, Bui, Linh T., Steven, Callori, Mark, Chaffin, Evgeny, Chichelnitskiy, Joshua, Chiou, Conlon, Thomas M., Cuoco, Michael S., Cuomo, Anna S. E., Marie, Deprez, Grant, Duclos, Denise, Fine, Fischer, David S., Shila, Ghazanfar, Astrid, Gillich, Bruno, Giotti, Joshua, Gould, Minzhe, Guo, Gutierrez, Austin J., Habermann, Arun C., Tyler, Harvey, Peng, He, Xiaomeng, Hou, Lijuan, Hu, Yan, Hu, Alok, Jaiswal, Lu, Ji, Peiyong, Jiang, Kapellos, Theodoros S., Kuo, Christin S., Ludvig, Larsson, Leney-Greene, Michael A., Kyungtae, Lim, Monika, Litviňuková, Ludwig, Leif S., Soeren, Lukassen, Wendy, Luo, Henrike, Maatz, Elo, Madissoon, Lira, Mamanova, Kasidet, Manakongtreecheep, Sylvie, Leroy, Mayr, Christoph H., Mbano, Ian M., Mcadams, Alexi M., Nabhan, Ahmad N., Nyquist, Sarah K., Lolita, Penland, Poirion, Olivier B., Sergio, Poli, Cancan, Qi, Rachel, Queen, Daniel, Reichart, Ivan, Rosas, Schupp, Jonas C., Shea, Conor V., Xingyi, Shi, Rahul, Sinha, Sit, Rene V., Kamil, Slowikowski, Michal, Slyper, Smith, Neal P., Alex, Sountoulidis, Maximilian, Strunz, Sullivan, Travis B., Dawei, Sun, Carlos, Talavera-López, Peng, Tan, Jessica, Tantivit, Travaglini, Kyle J., Tucker, Nathan R., Vernon, Katherine A., Wadsworth, Marc H., Julia, Waldman, Xiuting, Wang, Ke, Xu, Wenjun, Yan, William, Zhao, Ziegler, Carly G. K., The NHLBI LungMap Consortium, Zerti, Darin, The Human Cell Atlas Lung Biological Network, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
0301 basic medicine, Male, Cathepsin L, Respiratory System, Datasets as Topic, Lung/metabolism, Sequence Analysis, RNA/methods, Organ Specificity/genetics, 0302 clinical medicine, 80 and over, Respiratory system, Lung, COVID-19/epidemiology, Aged, 80 and over, Serine Endopeptidases, General Medicine, respiratory system, Middle Aged, Host-Pathogen Interactions/genetics, 3. Good health, Angiotensin-Converting Enzyme 2/genetics, medicine.anatomical_structure, Datasets as Topic/statistics & numerical data, Respiratory System/metabolism, Organ Specificity, Cathepsin L/genetics, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, Tumor necrosis factor alpha, Female, Angiotensin-Converting Enzyme 2, Single-Cell Analysis, RNA/methods, Sequence Analysis, Adult, Alveolar Epithelial Cells/metabolism, Serine Endopeptidases/genetics, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Immune system, Viral entry, Parenchyma, medicine, Humans, Gene Expression Profiling/statistics & numerical data, Aged, Demography, SARS-CoV-2, Sequence Analysis, RNA, Gene Expression Profiling, Single-Cell Analysis/methods, COVID-19, Virus Internalization, Gene expression profiling, 030104 developmental biology, Alveolar Epithelial Cells, Immunology, Tissue tropism, SARS-CoV-2/physiology
Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Full Text
View/download PDF

38. B-BIND: Biophysical Bayesian Inference for Neurodegenerative Dynamics.

Author

Agrawal A, Rachleff VM, Travaglini KJ, Mukherjee S, Crane PK, Hawrylycz M, Keene CD, Lein E, Mena GE, and Gabitto MI

Abstract

Throughout an organism's life, a multitude of complex and interdependent biological systems transition through biophysical processes that serve as indicators of the underlying biological states. Inferring these latent, unobserved states is a goal of modern biology and neuroscience. However, in many experimental setups, we can at best obtain discrete snapshots of the system at different times and for different individuals. This challenge is particularly relevant in the study of Alzheimer's Disease (AD) progression, where we observe the aggregation of pathology in brain donors, but the underlying disease state is unknown. This paper proposes a biophysically motivated Bayesian framework (B-BIND: Biophysical Bayesian Inference for Neurodegenerative Dynamics), where the disease state is modeled and continuously inferred from observed quantifications of multiple AD pathological proteins. Inspired by biophysical models, we describe pathological burden as an exponential process. The progression of AD is modeled by assigning a latent score, termed pseudotime, to each pathological state, creating a pseudotemporal order of donors based on their pathological burden. We study the theoretical properties of the model using linearization to reveal convergence and identifiability properties. We provide Markov chain Monte Carlo estimation algorithms, illustrating the effectiveness of our approach with multiple simulation studies across various data conditions. Applying this methodology to data from the Seattle Alzheimer's Disease Brain Cell Atlas, we infer the pseudotime ordering of donors. Finally, we analyze the information within each pathological feature to refine the model, focusing on the most informative pathologies. This framework lays the groundwork for continuous pseudotime modeling in the analysis of neurodegenerative diseases.

Published
2024
Full Text
View/download PDF

39. Single-cell genomics and regulatory networks for 388 human brains.

Author

Emani PS, Liu JJ, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee CY, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X, Bakken TE, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard JF, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman GE, Huang A, Jiang Y, Jin T, Jorstad NL, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran JR, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan AS, Riesenmy TR, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini KJ, Wamsley B, Wang G, Xia Y, Xiao S, Yang AC, Zheng S, Gandal MJ, Lee D, Lein ES, Roussos P, Sestan N, Weng Z, White KP, Won H, Girgenti MJ, Zhang J, Wang D, Geschwind D, and Gerstein M

Subjects
Humans, Aging genetics, Cell Communication genetics, Chromatin metabolism, Chromatin genetics, Genomics, Prefrontal Cortex metabolism, Prefrontal Cortex physiology, Quantitative Trait Loci, Brain metabolism, Gene Regulatory Networks, Mental Disorders genetics, Single-Cell Analysis
Abstract

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

Published
2024
Full Text
View/download PDF

40. Integrated multimodal cell atlas of Alzheimer's disease.

Author

Gabitto MI, Travaglini KJ, Rachleff VM, Kaplan ES, Long B, Ariza J, Ding Y, Mahoney JT, Dee N, Goldy J, Melief EJ, Brouner K, Campos J, Carr AJ, Casper T, Chakrabarty R, Clark M, Compos J, Cool J, Valera Cuevas NJ, Dalley R, Darvas M, Ding SL, Dolbeare T, Mac Donald CL, Egdorf T, Esposito L, Ferrer R, Gala R, Gary A, Gloe J, Guilford N, Guzman J, Ho W, Jarksy T, Johansen N, Kalmbach BE, Keene LM, Khawand S, Kilgore M, Kirkland A, Kunst M, Lee BR, Malone J, Maltzer Z, Martin N, McCue R, McMillen D, Meyerdierks E, Meyers KP, Mollenkopf T, Montine M, Nolan AL, Nyhus J, Olsen PA, Pacleb M, Pham T, Pom CA, Postupna N, Ruiz A, Schantz AM, Sorensen SA, Staats B, Sullivan M, Sunkin SM, Thompson C, Tieu M, Ting J, Torkelson A, Tran T, Wang MQ, Waters J, Wilson AM, Haynor D, Gatto N, Jayadev S, Mufti S, Ng L, Mukherjee S, Crane PK, Latimer CS, Levi BP, Smith K, Close JL, Miller JA, Hodge RD, Larson EB, Grabowski TJ, Hawrylycz M, Keene CD, and Lein ES

Abstract

Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org., Competing Interests: Additional Declarations: There is NO Competing Interest.

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results