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

Publication ,  Journal Article
Conchola, AS; Frum, T; Xiao, Z; Hsu, PP; Kaur, K; Downey, MS; Hein, RFC; Miller, AJ; Tsai, Y-H; Wu, A; Holloway, EM; Anand, A; Murthy, PKL ...
Published in: Proc Natl Acad Sci U S A
June 13, 2023

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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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

June 13, 2023

Volume

120

Issue

24

Start / End Page

e2210113120

Location

United States

Related Subject Headings

  • Stem Cells
  • Organoids
  • Lung
  • Humans
  • Epithelial Cells
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cell Lineage
  • Cell Differentiation
 

Citation

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Conchola, A. S., Frum, T., Xiao, Z., Hsu, P. P., Kaur, K., Downey, M. S., … Spence, J. R. (2023). Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung. Proc Natl Acad Sci U S A, 120(24), e2210113120. https://doi.org/10.1073/pnas.2210113120
Conchola, Ansley S., Tristan Frum, Zhiwei Xiao, Peggy P. Hsu, Kamika Kaur, Michael S. Downey, Renee F. C. Hein, et al. “Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung.Proc Natl Acad Sci U S A 120, no. 24 (June 13, 2023): e2210113120. https://doi.org/10.1073/pnas.2210113120.
Conchola AS, Frum T, Xiao Z, Hsu PP, Kaur K, Downey MS, et al. Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung. Proc Natl Acad Sci U S A. 2023 Jun 13;120(24):e2210113120.
Conchola, Ansley S., et al. “Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung.Proc Natl Acad Sci U S A, vol. 120, no. 24, June 2023, p. e2210113120. Pubmed, doi:10.1073/pnas.2210113120.
Conchola AS, Frum T, Xiao Z, Hsu PP, Kaur K, Downey MS, Hein RFC, Miller AJ, Tsai Y-H, Wu A, Holloway EM, Anand A, Murthy PKL, Glass I, Tata PR, Spence JR. Regionally distinct progenitor cells in the lower airway give rise to neuroendocrine and multiciliated cells in the developing human lung. Proc Natl Acad Sci U S A. 2023 Jun 13;120(24):e2210113120.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

June 13, 2023

Volume

120

Issue

24

Start / End Page

e2210113120

Location

United States

Related Subject Headings

  • Stem Cells
  • Organoids
  • Lung
  • Humans
  • Epithelial Cells
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cell Lineage
  • Cell Differentiation