A human fetal lung cell atlas uncovers proximal-distal gradients of differentiation and key regulators of epithelial fates
Peng He, Kyungtae Lim, Dawei Sun, J. Patrick Pett, Quitz Jeng, Krzysztof Polański, Ziqi Dong, Liam Bolt, Laura Richardson, Lira Mamanova, Monika Dabrowska, Anna Wilbrey-Clark, Elo Madissoon, Zewen Kelvin Tuong, Emma Dann, Chenqu Suo, Issac Goh, Masahiro Yoshida, Marko 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.