A molecular cell atlas of the human lung from single cell RNA sequencing
Kyle J. Travaglini, Ahmad N. Nabhan, Lolita Penland, Rahul Sinha, Astrid Gillich, Rene V. Sit, Stephen Chang, Stephanie D. Conley, Yasuo Mori, Jun Seita, Gerald J. Berry, Joseph B. Shrager, Ross J. Metzger, Christin S. Kuo, Norma Neff, Irving L. Weissman, Stephen R. Quake, Mark A. Krasnow
Abstract
Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles1,2,3,4,5,6,7,8,9, 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.
Datasets
1. Krasnow Lab Human Lung Cell Atlas, 10X
Metadata
channel
region
free_annotation
donor_id
sample
location
magnetic.selection
preparation.site
compartment
tissue_ontology_term_id
assay_ontology_term_id
disease_ontology_term_id
development_stage_ontology_term_id
cell_type_ontology_term_id
self_reported_ethnicity_ontology_term_id
sex_ontology_term_id
organism_ontology_term_id
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tissue_type
cell_type
assay
disease
organism
sex
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self_reported_ethnicity
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Capillary Aerocyte4352 cells Alveolar Epithelial Type 23814 cells CD4+ Memory/Effector T3013 cells Classical Monocyte2077 cells Basophil/Mast 11350 cells Alveolar Fibroblast1296 cells CD8+ Memory/Effector T1190 cells Alveolar Epithelial Type 1972 cells Nonclassical Monocyte804 cells Airway Smooth Muscle693 cells Signaling Alveolar Epithelial Type 2669 cells Capillary Intermediate 1628 cells Adventitial Fibroblast557 cells Vascular Smooth Muscle469 cells Capillary Intermediate 2464 cells Bronchial Vessel 1455 cells Natural Killer T335 cells IGSF21+ Dendritic280 cells Myeloid Dendritic Type 2266 cells Differentiating Basal265 cells Bronchial Vessel 2235 cells Proliferating Macrophage226 cells OLR1+ Classical Monocyte207 cells Intermediate Monocyte188 cells TREM2+ Dendritic159 cells Plasmacytoid Dendritic137 cells Myeloid Dendritic Type 1131 cells Proliferating NK/T105 cells Proximal Ciliated88 cells Proliferating Basal47 cells Platelet/Megakaryocyte40 cells immune and endothelial17813 cells UBERON:000204860993 cells HsapDv:000014028793 cells HsapDv:000014527125 cells NCBITaxon:960665662 cells alveolar macrophage14734 cells capillary endothelial cell7391 cells endothelial cell6134 cells natural killer cell4769 cells type II pneumocyte3814 cells effector memory CD4-positive, alpha-beta T cell3013 cells classical monocyte2077 cells naive thymus-derived CD8-positive, alpha-beta T cell2042 cells myeloid leukocyte1902 cells endothelial cell of artery1484 cells lung ciliated cell1321 cells effector memory CD8-positive, alpha-beta T cell1190 cells vein endothelial cell1155 cells type I pneumocyte972 cells naive thymus-derived CD4-positive, alpha-beta T cell932 cells non-classical monocyte804 cells bronchial smooth muscle cell693 cells respiratory basal cell593 cells mucus secreting cell491 cells vascular associated smooth muscle cell469 cells endothelial cell of lymphatic vessel467 cells mature NK T cell335 cells CD1c-positive myeloid dendritic cell266 cells myofibroblast cell248 cells intermediate monocyte188 cells lung goblet cell159 cells plasmacytoid dendritic cell, human137 cells myeloid dendritic cell, human131 cells pulmonary interstitial fibroblast35 cells mesothelial cell of pleura29 cells tracheobronchial serous cell24 cells pulmonary ionocyte22 cells lung neuroendocrine cell11 cells 46-year-old human stage28793 cells 51-year-old human stage27125 cells 75-year-old human stage9744 cells 2. Krasnow Lab Human Lung Cell Atlas, Smart-seq2
Metadata
plate.barcode
region
label
sorter
sort.location
sample
location
donor_id
gating
free_annotation
compartment
tissue_ontology_term_id
disease_ontology_term_id
development_stage_ontology_term_id
assay_ontology_term_id
cell_type_ontology_term_id
self_reported_ethnicity_ontology_term_id
sex_ontology_term_id
organism_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
ahmad/kyle/lolita5422 cells Alveolar Epithelial Type 2760 cells Capillary Aerocyte622 cells Alveolar Epithelial Type 1421 cells Alveolar Fibroblast360 cells Airway Smooth Muscle346 cells Signaling Alveolar Epithelial Type 2201 cells Vascular Smooth Muscle176 cells Adventitial Fibroblast158 cells CD4+ Memory/Effector T126 cells Bronchial Vessel 1106 cells Classical Monocyte106 cells Capillary Intermediate 188 cells CD8+ Memory/Effector T59 cells Differentiating Basal43 cells Nonclassical Monocyte27 cells Proliferating NK/T17 cells Plasmacytoid Dendritic13 cells Myeloid Dendritic Type 27 cells Intermediate Monocyte6 cells natural killer cell1232 cells capillary endothelial cell872 cells endothelial cell816 cells type II pneumocyte760 cells lung ciliated cell551 cells type I pneumocyte421 cells naive thymus-derived CD8-positive, alpha-beta T cell378 cells bronchial smooth muscle cell346 cells respiratory basal cell240 cells lung goblet cell233 cells vascular associated smooth muscle cell176 cells naive thymus-derived CD4-positive, alpha-beta T cell131 cells effector memory CD4-positive, alpha-beta T cell126 cells classical monocyte106 cells endothelial cell of artery92 cells effector memory CD8-positive, alpha-beta T cell59 cells lung neuroendocrine cell55 cells myofibroblast cell52 cells myeloid leukocyte46 cells endothelial cell of lymphatic vessel44 cells vein endothelial cell42 cells alveolar macrophage32 cells non-classical monocyte27 cells pulmonary interstitial fibroblast20 cells plasmacytoid dendritic cell, human13 cells dendritic cell, human10 cells CD1c-positive myeloid dendritic cell7 cells intermediate monocyte6 cells pulmonary ionocyte2 cells 75-year-old human stage3987 cells 46-year-old human stage3273 cells 51-year-old human stage2149 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/5d445965-6f1a-4b68-ba3a-b8f765155d3a
Alias names
EGAS00001004344, PRJNA632939, HLCA, syn21041850, PMID33208946, PMC7704697
Cite this study
Travaglini, K.J., Nabhan, A.N., Penland, L., Sinha, R., Gillich, A., Sit, R.V., Chang, S., Conley, S.D., Mori, Y., Seita, J. and Berry, G.J., 2020. A molecular cell atlas of the human lung from single-cell RNA sequencing. Nature, 587(7835), pp.619-625. https://doi.org/10.1038/s41586-020-2922-4
