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Basal cells as stem cells of the mouse trachea and human airway epithelium.

The pseudostratified epithelium of the mouse trachea and human airways contains a population of basal cells expressing Trp-63 (p63) and cytokeratins 5 (Krt5) and Krt14. Using a KRT5-CreER(T2) transgenic mouse line for lineage tracing, we show that basal cells generate differentiated cells during postnatal growth and in the adult during both steady state and epithelial repair. We have fractionated mouse basal cells by FACS and identified 627 genes preferentially expressed in a basal subpopulation vs. non-BCs. Analysis reveals potential mechanisms regulating basal cells and allows comparison with other epithelial stem cells. To study basal cell behaviors, we describe a simple in vitro clonal sphere-forming assay in which mouse basal cells self-renew and generate luminal cells, including differentiated ciliated cells, in the absence of stroma. The transcriptional profile identified 2 cell-surface markers, ITGA6 and NGFR, which can be used in combination to purify human lung basal cells by FACS. Like those from the mouse trachea, human airway basal cells both self-renew and generate luminal daughters in the sphere-forming assay.

Pubmed ID: 19625615

Authors

  • Rock JR
  • Onaitis MW
  • Rawlins EL
  • Lu Y
  • Clark CP
  • Xue Y
  • Randell SH
  • Hogan BL

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 4, 2009

Associated Grants

  • Agency: NHLBI NIH HHS, Id: 2T32HL007538-26
  • Agency: NHLBI NIH HHS, Id: HL071303
  • Agency: NCI NIH HHS, Id: K12 CA100639-0
  • Agency: NHLBI NIH HHS, Id: R01 HL071303
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • Humans
  • Lung
  • Male
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Receptor, Nerve Growth Factor
  • Stem Cells
  • Trachea