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...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) Vol. 587; no. 7835; pp. 619 - 625
Main Authors: 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.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 26.11.2020
Nature Publishing Group
Subjects:
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography: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