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

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


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.

MeSH terms

  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Colitis / chemically induced
  • Colitis / pathology
  • Dextran Sulfate
  • Diphtheria Toxin / pharmacology
  • Dose-Response Relationship, Radiation
  • Hyperplasia
  • Intestines / drug effects
  • Intestines / physiology*
  • Intestines / radiation effects*
  • Mice
  • Models, Animal
  • Paneth Cells / cytology
  • Paneth Cells / drug effects
  • Paneth Cells / radiation effects
  • Radiation, Ionizing*
  • Receptors, G-Protein-Coupled / metabolism*
  • Regeneration* / drug effects
  • Regeneration* / radiation effects
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / radiation effects


  • Adenomatous Polyposis Coli Protein
  • Diphtheria Toxin
  • Lgr5 protein, mouse
  • Receptors, G-Protein-Coupled
  • Dextran Sulfate