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. 2014 Feb 6;14(2):149-59.
doi: 10.1016/j.stem.2013.11.008. Epub 2013 Dec 12.

Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration

Ciara Metcalfe  1 , Noelyn M Kljavin  1 , Ryan Ybarra  1 , Frederic J de Sauvage  2
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Free article

Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration

Ciara Metcalfe et al. Cell Stem Cell. .
Free article

Abstract

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.

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