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

Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 – 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 d...

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Vydáno v:	Nature (London) Ročník 587; číslo 7835; s. 619 - 625
Hlavní autoři:	Travaglini, Kyle J., Nabhan, Ahmad N., Penland, Lolita, Sinha, Rahul, Gillich, Astrid, Sit, Rene V., Chang, Stephen, Conley, Stephanie D., Mori, Yasuo, Seita, Jun, Berry, Gerald J., Shrager, Joseph B., Metzger, Ross J., Kuo, Christin S., Neff, Norma, Weissman, Irving L., Quake, Stephen R., Krasnow, Mark A.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 26.11.2020 Nature Publishing Group
Témata:	13/1 13/31 13/51 14/1 14/19 14/32 38/32 38/39 38/77 38/91 631/181/2474 631/208/199 631/208/212/2019 631/337/2019 64/110 64/60 82/1 Aged Analysis Animals Annotations Atlases as Topic Biomarkers Blood Blood circulation Cell Communication Cell cycle Cells Cells - classification Cells - immunology Cells - metabolism Chemokines - metabolism Endothelial Cells - metabolism Epithelial Cells - metabolism Evolution Female Fibroblasts Gene expression Gene sequencing Genomes Hormones Humanities and Social Sciences Humans Identification and classification Immune system Immunity Lung - cytology Lung - immunology Lung diseases Lungs Male Methods Mice Middle Aged Molecular biology multidisciplinary Organs Physiological aspects Quorum sensing Receptors, Lymphocyte Homing - metabolism Ribonucleic acid RNA RNA sequencing Science Science (multidisciplinary) Sequence Analysis, RNA Signal Transduction Single-Cell Analysis Stromal Cells - metabolism Switches Tissue engineering Transcription factors Transcriptome - genetics United States
ISSN:	0028-0836, 1476-4687, 1476-4687
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Popis
Shrnutí:	Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 – 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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Present address: Calico Life Sciences, South San Francisco, CA USA (L.P.). Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan (Y.S.). Medical Sciences Innovation Hub Program, RIKEN, Japan (J.S.). K.J.T., A.N.N., L.P., R.S., A.G., C.S.K., R.J.M., and M.A.K. conceived the project and designed the lung and blood cell isolation strategy, J.B.S. and C.S.K. designed clinical protocols, reviewed clinical histories and coordinated patient care teams to obtain profiled tissues, G.B. provided expert clinical evaluation and micrographs of donor tissue histology, K.J.T., A.N.N., R.S., and A.G. processed tissue to single cell suspensions, K.J.T., A.N.N., L.P. A.G., R.S., S.D.C. sorted cells for SS2, A.N.N., L.P., S.C., and R.V.S. prepared sequencing libraries, and K.J.T., R.V.S. and L.P. processed and aligned sequencing data. R.S., J.S., and Y.M. performed and supervised bulk mRNA sequencing on defined immune populations. K.J.T., A.N.N., R.S. A.G., and R.J.M. provided tissue expertise and annotated cell types. K.J.T., A.N.N., and M.A.K. designed and implemented bioinformatic methods and interpreted results. K.J.T., A.N.N., and A.G. performed follow up stains. M.A.K., S.R.Q., N.F.N., I.L.W., C.S.K., and R.J.M. supervised and supported the work. K.J.T., A.N.N., and M.A.K. wrote the manuscript, and all authors reviewed and edited the manuscript. These authors contributed equally and will list themselves first on their CVs. Author Contributions
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-020-2922-4