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

人类胎肺细胞图谱揭示了分化的近端-远端梯度和上皮细胞命运的关键调控因子

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作者: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

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.

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