期刊
DEVELOPMENTAL CELL
卷 53, 期 1, 页码 117-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2020.01.033
关键词
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资金
- Chan Zuckerberg Initiative Human Cell Atlas Seed Network grant
- NIH-NHLBI [R01HL119215]
- Cystic Fibrosis Foundation Therapeutics Epithelial Stem Cell Consortium
- Ruth L. Kirschstein Predoctoral Individual National Research Service Award [NIH-NHLBI F31HL142197]
- Training Program in Basic and Translational Digestive Sciences NIH-NIDDK [T32DK094775]
- Cellular and Biotechnology Training Program NIH-NIGMS [T32GM008353]
- Training Program in Organogenesis Fellowship NIH-NICHD [T32HD007505]
- NIH-NICHD [R24HD000836]
Bud tip progenitor cells give rise to all murine lung epithelial lineages and have been described in the developing human lung; however, the mechanisms controlling human bud tip differentiation into specific lineages are unclear. Here, we used homogeneous human bud tip organoid cultures and identified SMAD signaling as a key regulator of the bud tip-to-airway transition. SMAD induction led to the differentiation of airway-like organoids possessing functional basal cells capable of clonal expansion and multilineage differentiation. To benchmark in vitro-derived organoids, we developed a single-cell mRNA sequencing atlas of the human lung from 11.5 to 21 weeks of development, which revealed high degrees of similarity between the in vitro-derived and in vivo airway. Together, this work sheds light on human airway differentiation in vitro and provides a single-cell atlas of the developing human lung.
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