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Krt19(+)/Lgr5(−) cells are radioresistant cancer initiating stem cells in the colon and intestine
Cell Stem Cell (2015)
  • Samuel Asfaha, Western University
  • Y Hayakawa
  • A Muley
  • S Stokes
  • TA Graham
  • RE Ericksen
  • CB Westphalen
  • J von Burstin
  • TL Mastracci
  • DL Worthley
  • C Guha
  • M Quante
  • AK Rustgi
  • TC Wang
The colonic and intestinal epithelium are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt based columnar (CBC) Lgr5+ cells, while the second is comprised of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5-negative stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament, keratin-19 (Krt19), marks long-lived, radiation resistant cells above the crypt base that generate Lgr5+ CBCs in the colon and intestine. In colorectal cancer models, Krt19+ cancer initiating cells are also radioresistant while Lgr5+ stem cells are radiosensitive. Moreover, Lgr5+ stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5+ stem cells results in their regeneration from Krt19 expressing cells. Thus, Krt19+ stem cells are a discrete target relevant for cancer therapy.
  • Krt19,
  • intestine,
  • colon,
  • stem cells,
  • cancer
Publication Date
Citation Information
Samuel Asfaha, Y Hayakawa, A Muley, S Stokes, et al.. "Krt19(+)/Lgr5(−) cells are radioresistant cancer initiating stem cells in the colon and intestine" Cell Stem Cell (2015)
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