A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates

Peng He; Kyungtae Lim; Dawei Sun; Jan Patrick Pett; Quitz Jeng; Krzysztof Polanski; Ziqi Dong; Liam Bolt; Laura Richardson; Lira Mamanova; Monika Dabrowska; Anna Wilbrey-Clark; Elo Madissoon; Zewen Kelvin Tuong; Emma Dann; Chenqu Suo; Isaac Goh; Masahiro Yoshida; Marko Z Nikolić; Sam M Janes; Xiaoling He; Roger A Barker; Sarah A Teichmann; John C Marioni; Kerstin B Meyer; Emma L Rawlins

doi:10.1016/j.cell.2022.11.005

A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates

Cell. 2022 Dec 8;185(25):4841-4860.e25. doi: 10.1016/j.cell.2022.11.005.

Authors

Peng He¹, Kyungtae Lim², Dawei Sun², Jan Patrick Pett³, Quitz Jeng², Krzysztof Polanski³, Ziqi Dong², Liam Bolt³, Laura Richardson³, Lira Mamanova³, Monika Dabrowska³, Anna Wilbrey-Clark³, Elo Madissoon¹, Zewen Kelvin Tuong⁴, Emma Dann³, Chenqu Suo⁵, Isaac Goh⁶, Masahiro Yoshida⁷, Marko Z Nikolić⁷, Sam M Janes⁷, Xiaoling He⁸, Roger A Barker⁸, Sarah A Teichmann⁹, John C Marioni¹⁰, Kerstin B Meyer³, Emma L Rawlins¹¹

Affiliations

¹ Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK.
² Wellcome Trust/CRUK Gurdon Institute, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK.
³ Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
⁴ Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Molecular Immunity Unit, University of Cambridge Department of Medicine, Cambridge, UK.
⁵ Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Department of Paediatrics, Cambridge University Hospitals, Hills Road, Cambridge CB2 0 QQ, UK.
⁶ Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
⁷ Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
⁸ John van Geest Centre for Brain Repair, Department of Clinical Neurosciences and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
⁹ Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; Department of Physics, Cavendish Laboratory, University of Cambridge, Cambridge CB3 0HE, UK.
¹⁰ Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
¹¹ Wellcome Trust/CRUK Gurdon Institute, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: e.rawlins@gurdon.cam.ac.uk.

PMID: 36493756
DOI: 10.1016/j.cell.2022.11.005

Abstract

We present a multiomic cell atlas of human lung development that combines single-cell RNA and ATAC sequencing, high-throughput spatial transcriptomics, and single-cell imaging. Coupling single-cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial, and erythrocyte/leukocyte compartments from 5-22 post-conception weeks. We identify previously uncharacterized cell states in all compartments. These include developmental-specific secretory progenitors and a subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). To illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signaling and transcription factor hierarchies which we rigorously test using organoid models.

Keywords: differentiation; epigenetics; fibroblast; genomics; multiomic; organoids; perturbation; single-cell; spatial; transcription factor.

MeSH terms

Atlases as Topic
Cell Differentiation
Fetus* / cytology
Gene Expression Profiling
Humans
Lung* / cytology
Organogenesis
Organoids

Abstract

MeSH terms

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