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In vitro and in vivo development of the human airway at single-cell resolution

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Treutlein,  Barbara
Single Cell Genomics, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Camp,  J. Gray
Modern and Archaic Human Cell Biology, Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Citation

Miller, A. J., Yu, Q., Czerwinski, M., Tsai, Y.-H., Conway, R. F., Wu, A., et al. (2020). In vitro and in vivo development of the human airway at single-cell resolution. Developmental Cell, 53(1): e6, pp. 117-128. doi:10.1016/j.devcel.2020.01.033.


Cite as: http://hdl.handle.net/21.11116/0000-0006-42EC-6
Abstract
Summary 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.