Format

Send to

Choose Destination
Cell Rep. 2018 Jan 23;22(4):1003-1015. doi: 10.1016/j.celrep.2017.12.093. Epub 2018 Jan 28.

Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation.

Author information

1
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
2
Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
3
Departments of Orofacial Sciences and Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
5
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA; Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: mestes@bcm.edu.

Abstract

Intestinal stem cells (ISCs) maintain and repair the intestinal epithelium. While regeneration after ISC-targeted damage is increasingly understood, injury-repair mechanisms that direct regeneration following injuries to differentiated cells remain uncharacterized. The enteric pathogen, rotavirus, infects and damages differentiated cells while sparing all ISC populations, thus allowing the unique examination of the response of intact ISC compartments during injury-repair. Upon rotavirus infection in mice, ISC compartments robustly expand and proliferating cells rapidly migrate. Infection results specifically in stimulation of the active crypt-based columnar ISCs, but not alternative reserve ISC populations, as is observed after ISC-targeted damage. Conditional ablation of epithelial WNT secretion diminishes crypt expansion and ISC activation, demonstrating a previously unknown function of epithelial-secreted WNT during injury-repair. These findings indicate a hierarchical preference of crypt-based columnar cells (CBCs) over other potential ISC populations during epithelial restitution and the importance of epithelial-derived signals in regulating ISC behavior.

KEYWORDS:

ISC; RV; epithelial WNT; intestinal stem cell; regeneration; rotavirus

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center