Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating

Stem Cell Reports. 2018 Jun 5;10(6):1947-1958. doi: 10.1016/j.stemcr.2018.04.022. Epub 2018 May 24.


Two principal stem cell pools orchestrate the rapid cell turnover in the intestinal epithelium. Rapidly cycling Lgr5+ stem cells are intercalated between the Paneth cells at the crypt base (CBCs) and injury-resistant reserve stem cells reside above the crypt base. The intermediate filament Keratin 15 (Krt15) marks either stem cells or long-lived progenitor cells that contribute to tissue repair in the hair follicle or the esophageal epithelium. Herein, we demonstrate that Krt15 labels long-lived and multipotent cells in the small intestinal crypt by lineage tracing. Krt15+ crypt cells display self-renewal potential in vivo and in 3D organoid cultures. Krt15+ crypt cells are resistant to high-dose radiation and contribute to epithelial regeneration following injury. Notably, loss of the tumor suppressor Apc in Krt15+ cells leads to adenoma and adenocarcinoma formation. These results indicate that Krt15 marks long-lived, multipotent, and injury-resistant crypt cells that may function as a cell of origin in intestinal cancer.

Keywords: intestinal crypts; keratin 15; radiation injury; stem cells; tumor.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation
  • Cell Proliferation
  • Cell Self Renewal
  • Cell Transformation, Neoplastic* / metabolism
  • Dose-Response Relationship, Radiation
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Intestinal Mucosa / cytology*
  • Keratin-15 / metabolism*
  • Mice
  • Paneth Cells / cytology
  • Paneth Cells / metabolism
  • Paneth Cells / radiation effects
  • Radiation Tolerance*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / radiation effects*


  • Biomarkers
  • Keratin-15