First Author | Giroux V | Year | 2018 |
Journal | Stem Cell Reports | Volume | 10 |
Issue | 6 | Pages | 1947-1958 |
PubMed ID | 29805107 | Mgi Jnum | J:305912 |
Mgi Id | MGI:6708382 | Doi | 10.1016/j.stemcr.2018.04.022 |
Citation | Giroux V, et al. (2018) Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating. Stem Cell Reports 10(6):1947-1958 |
abstractText | 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. |