First Author | Metcalfe C | Year | 2014 |
Journal | Cell Stem Cell | Volume | 14 |
Issue | 2 | Pages | 149-59 |
PubMed ID | 24332836 | Mgi Jnum | J:210107 |
Mgi Id | MGI:5569568 | Doi | 10.1016/j.stem.2013.11.008 |
Citation | Metcalfe C, et al. (2014) Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell 14(2):149-59 |
abstractText | The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Lgr5 marks 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. |