Journal
STEM CELL REPORTS
Volume 10, Issue 6, Pages 1947-1958Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.04.022
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Funding
- NCI [P01-CA098101]
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Center of Molecular Studies in Digestive and Liver Diseases, NIH [P30-DK050306, R01-DK056645]
- American Cancer Society
- Fonds de recherche en sante du Quebec [P-Giroux-27692, P-Giroux-31601]
- NIH NIDDK [K01-DK100485]
- Crohn's and Colitis Foundation Career Development Award
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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 highdose 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.
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