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


ABSTRACT: 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.

SUBMITTER: Giroux V 

PROVIDER: S-EPMC5993649 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Giroux Véronique V   Stephan Julien J   Chatterji Priya P   Rhoades Ben B   Wileyto E Paul EP   Klein-Szanto Andres J AJ   Lengner Christopher J CJ   Hamilton Kathryn E KE   Rustgi Anil K AK  

Stem cell reports 20180524 6


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  ...[more]

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2008-06-27 | GSE8863 | GEO