Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations.

Published

Journal Article

Following injury, stem cells restore normal tissue architecture by producing the proper number and proportions of differentiated cells. Current models of airway epithelial regeneration propose that distinct cytokeratin 8-expressing progenitor cells, arising from p63(+) basal stem cells, subsequently differentiate into secretory and ciliated cell lineages. We now show that immediately following injury, discrete subpopulations of p63(+) airway basal stem/progenitor cells themselves express Notch pathway components associated with either secretory or ciliated cell fate commitment. One basal cell population displays intracellular Notch2 activation and directly generates secretory cells; the other expresses c-myb and directly yields ciliated cells. Furthermore, disrupting Notch ligand activity within the basal cell population at large disrupts the normal pattern of lineage segregation. These non-cell-autonomous effects demonstrate that effective airway epithelial regeneration requires intercellular communication within the broader basal stem/progenitor cell population. These findings have broad implications for understanding epithelial regeneration and stem cell heterogeneity.

Full Text

Duke Authors

Cited Authors

  • Pardo-Saganta, A; Law, BM; Tata, PR; Villoria, J; Saez, B; Mou, H; Zhao, R; Rajagopal, J

Published Date

  • February 2015

Published In

Volume / Issue

  • 16 / 2

Start / End Page

  • 184 - 197

PubMed ID

  • 25658372

Pubmed Central ID

  • 25658372

Electronic International Standard Serial Number (EISSN)

  • 1875-9777

International Standard Serial Number (ISSN)

  • 1934-5909

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2015.01.002

Language

  • eng