Cell Stem Cell
Volume 14, Issue 2, 6 February 2014, Pages 149-159
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Article
Lgr5+ Stem Cells Are Indispensable for Radiation-Induced Intestinal Regeneration

https://doi.org/10.1016/j.stem.2013.11.008Get rights and content
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Highlights

  • Simultaneous ablation of Lgr5+ cells with irradiation results in severe crypt loss

  • Radiation inhibits the recovery of Lgr5+ cells after DT-induced ablation

  • Depletion of Lgr5+ cells in Apc-deficient crypts does not suppress hyperplasia

Summary

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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