ISCC Labs Published in Cell Reports

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ISCC Labs Published in Cell Reports

Intestinal stem cells (ISCs) maintain and repair the
intestinal epithelium. While regeneration after ISCtargeted
damage is increasingly understood, injuryrepair
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 epithelialWNT 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.

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