Mouse Intestinal Krt15+ Crypt Cells Are Radio-Resistant and Tumor Initiating.
Stem Cell Reports
; 10(6): 1947-1958, 2018 06 05.
Article
em En
| MEDLINE
| ID: mdl-29805107
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tolerância a Radiação
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Células-Tronco
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Transformação Celular Neoplásica
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Queratina-15
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Mucosa Intestinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article