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

Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet- and plate-based single cell RNA sequencing applied to ~75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, 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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006126 Illumina NovaSeq 6000 NextSeq 500 3
EGAD00001006127 Illumina NovaSeq 6000 NextSeq 500 3
EGAD00001006128 Illumina NovaSeq 6000 NextSeq 500 3
Publications Citations
A molecular cell atlas of the human lung from single-cell RNA sequencing.
Nature 587: 2020 619-625
733
T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours.
Nat Biomed Eng 5: 2021 1246-1260
77
Specific splice junction detection in single cells with SICILIAN.
Genome Biol 22: 2021 219
8
Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms.
Cancer Cell 39: 2021 1531-1547.e10
106
The SpliZ generalizes 'percent spliced in' to reveal regulated splicing at single-cell resolution.
Nat Methods 19: 2022 307-310
14
A single-cell regulatory map of postnatal lung alveologenesis in humans and mice.
Cell Genom 2: 2022 100108
14
From COVID to fibrosis: lessons from single-cell analyses of the human lung.
Hum Genomics 16: 2022 20
9
Lung fibroblasts facilitate pre-metastatic niche formation by remodeling the local immune microenvironment.
Immunity 55: 2022 1483-1500.e9
61
ReadZS detects cell type-specific and developmentally regulated RNA processing programs in single-cell RNA-seq.
Genome Biol 23: 2022 226
4
Altered host protease determinants for SARS-CoV-2 Omicron.
Sci Adv 9: 2023 eadd3867
16
Decision level integration of unimodal and multimodal single cell data with scTriangulate.
Nat Commun 14: 2023 406
5
Single-cell RNA sequencing reveals the developmental program underlying proximal-distal patterning of the human lung at the embryonic stage.
Cell Res 33: 2023 421-433
13
β-Catenin signaling in alveolar macrophages enhances lung metastasis through a TNF-dependent mechanism.
JCI Insight 8: 2023 e160978
10
Convergence of YAP/TAZ, TEAD and TP63 activity is associated with bronchial premalignant severity and progression.
J Exp Clin Cancer Res 42: 2023 116
6
An integrated cell atlas of the lung in health and disease.
Nat Med 29: 2023 1563-1577
151
DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner.
PLoS Biol 21: 2023 e3002097
9
Complement C1q essential for aeroallergen sensitization via CSF1R<sup>+</sup> conventional dendritic cells type 2.
J Allergy Clin Immunol 152: 2023 1141-1152.e2
3
A single-cell atlas of in vitro multiculture systems uncovers the in vivo lineage trajectory and cell state in the human lung.
Exp Mol Med 55: 2023 1831-1842
3
Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.
Am J Respir Cell Mol Biol 70: 2024 26-38
1
scTOP: physics-inspired order parameters for cellular identification and visualization.
Development 150: 2023 dev201873
4
Collagen type XIV is proportionally lower in the lung tissue of patients with IPF.
Sci Rep 13: 2023 19393
2
MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution.
J Clin Invest 134: 2024 e172826
2
Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation.
Viruses 16: 2024 1049
0