Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung.

Abstract

Using scRNA-seq and microscopy, we describe a cell that is enriched in the lower airways of the developing human lung and identified by the unique coexpression of SCGB3A2/SFTPB/CFTR. To functionally interrogate these cells, we apply a single-cell barcode-based lineage tracing method, called CellTagging, to track the fate of SCGB3A2/SFTPB/CFTR cells during airway organoid differentiation in vitro. Lineage tracing reveals that these cells have a distinct differentiation potential from basal cells, giving rise predominantly to pulmonary neuroendocrine cells and a subset of multiciliated cells distinguished by high C6 and low MUC16 expression. Lineage tracing results are supported by studies using organoids and isolated cells from the lower noncartilaginous airway. We conclude that SCGB3A2/SFTPB/CFTR cells are enriched in the lower airways of the developing human lung and contribute to the epithelial diversity and heterogeneity in this region.

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10.1073/pnas.2210113120

Publication Info

Conchola, Ansley S, Tristan Frum, Zhiwei Xiao, Peggy P Hsu, Kamika Kaur, Michael S Downey, Renee FC Hein, Alyssa J Miller, et al. (2023). Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung. Proceedings of the National Academy of Sciences of the United States of America, 120(24). p. e2210113120. 10.1073/pnas.2210113120 Retrieved from https://hdl.handle.net/10161/29039.

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Tata

Purushothama Rao Tata

Associate Professor of Cell Biology

Lung regeneration
Lung stem cells
Cell plasticity
Organoid models
Lung Fibrosis
Single Cell Biology


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