Lgr5+Stem Cells Are Indispensable for Radiation-Induced Intestinal Regeneration

Autor: Metcalfe, Ciara, Kljavin, Noelyn M., Ybarra, Ryan, de Sauvage, Frederic J.
Zdroj: Cell Stem Cell; February 2014, Vol. 14 Issue: 2 p149-159, 11p
Abstrakt: The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5marks mitotically active intestinal stem cells (ISCs). Importantly, intestinal homeostasis can be maintained after depletion of Lgr5+cells due to the activation of Lgr5−reserve ISCs. The Lgr5−ISC populations are thought to play a similar role during intestinal regeneration following radiation-induced damage. We tested this regeneration hypothesis by combining depletion of Lgr5+ISCs with radiation exposure. In contrast to the negligible effect of Lgr5+ISC loss during homeostasis, depletion of Lgr5+cells during radiation-induced damage and subsequent repair caused catastrophic crypt loss and deterioration of crypt-villus architecture. Interestingly though, we found that crypts deficient for Lgr5+cells are competent to undergo hyperplasia upon loss of Apc. These data argue that Lgr5−reserve stem cells are radiosensitive and that Lgr5+cells are crucial for robust intestinal regeneration following radiation exposure but are dispensable for premalignant hyperproliferation.
Databáze: Supplemental Index