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

Accepted version
Peer-reviewed

Type

Article

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Authors

He, Peng 
Lim, Kyungtae 
Sun, Dawei 
Pett, Jan Patrick 
Jeng, Quitz 

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.

Description

Keywords

differentiation, epigenetics, fibroblast, genomics, multiomic, organoids, perturbation, single-cell, spatial, transcription factor, Humans, Cell Differentiation, Gene Expression Profiling, Lung, Organogenesis, Organoids, Atlases as Topic, Fetus

Journal Title

Cell

Conference Name

Journal ISSN

0092-8674
1097-4172

Volume Title

Publisher

Elsevier BV
Sponsorship
Medical Research Council (MR/P009581/1)
Wellcome Trust (092096/Z/10/Z)
Medical Research Council (MR/S035907/1)
Wellcome Trust (109146/Z/15/Z)
Cancer Research UK (C6946/A24843)
Wellcome Trust (203144/Z/16/Z)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (MC_PC_17230)
Medical Research Council (MR/R015635/1)
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