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

人类胎儿肺细胞图谱揭示近端-远端分化梯度和上皮命运的关键调节因子

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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, Xiaoli

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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