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

Publication date: Available online 24 May 2018 Source:Stem Cell Reports Author(s): Véronique Giroux, Julien Stephan, Priya Chatterji, Ben Rhoades, E. Paul Wileyto, Andres J. Klein-Szanto, Christopher J. Lengner, Kathryn E. Hamilton, Anil K. Rustgi 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. Teaser In this article, Rustgi and colleagues identify a new population of long-lived cells within the intestinal crypt, marked by the Krt15 promoter. Krt15+ cells are self-renewing, multipotent, and ...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research