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

Cell Stem Cell. 2015 Feb 5;16(2):184-97. doi: 10.1016/j.stem.2015.01.002.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage*
  • Cells, Cultured
  • Chlorine
  • Doxycycline
  • Mice
  • Respiratory Mucosa / cytology*
  • Respiratory Mucosa / metabolism
  • Stem Cells / cytology*
  • Sulfur Dioxide
  • Wounds and Injuries / chemically induced
  • Wounds and Injuries / therapy*


  • Sulfur Dioxide
  • Chlorine
  • Doxycycline