Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable.

Nature | Sep 18, 2011

The small intestine epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base. However, the relative functions of these two pools and their interrelationship are not understood. Here we specifically ablated Lgr5-expressing cells in mice using a human diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the epithelium, indicating that other cell types can compensate for the elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, indicating that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis, and that in the absence of these cells, Bmi1-expressing cells can serve as an alternative stem cell pool. These data provide the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the small intestine epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions.

Pubmed ID: 21927002 RIS Download

Mesh terms: Animals | Cell Lineage | Epithelial Cells | Female | Heparin-binding EGF-like Growth Factor | Homeostasis | Humans | Intercellular Signaling Peptides and Proteins | Intestine, Small | Male | Mice | Mice, Inbred C57BL | Nuclear Proteins | Polycomb Repressive Complex 1 | Proto-Oncogene Proteins | Receptors, G-Protein-Coupled | Regeneration | Repressor Proteins | Stem Cells

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

Associated grants

  • Agency: NIH HHS, Id: DP2 OD007191
  • Agency: NIDCR NIH HHS, Id: R01 DE021420
  • Agency: NIH HHS, Id: 1-DP2-OD007191
  • Agency: NIDCR NIH HHS, Id: R01-DE021420

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.