A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable
- PMID: 21927002
- PMCID: PMC4251967
- DOI: 10.1038/nature10408
A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable
Erratum in
- Nature. 2012 Feb 2;482(7383):120
Abstract
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.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4251967/bin/nihms643813f1.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4251967/bin/nihms643813f2.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4251967/bin/nihms643813f3.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4251967/bin/nihms643813f4.gif)
Comment in
-
Tales from the crypt: the expanding role of slow cycling intestinal stem cells.Cell Stem Cell. 2012 Jan 6;10(1):2-4. doi: 10.1016/j.stem.2011.12.012. Cell Stem Cell. 2012. PMID: 22226346 Free PMC article.
Similar articles
-
The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations.Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):466-71. doi: 10.1073/pnas.1118857109. Epub 2011 Dec 21. Proc Natl Acad Sci U S A. 2012. PMID: 22190486 Free PMC article.
-
Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells.Cell. 2024 Jun 6;187(12):3039-3055.e14. doi: 10.1016/j.cell.2024.05.001. Cell. 2024. PMID: 38848677
-
SOX9 maintains reserve stem cells and preserves radioresistance in mouse small intestine.Gastroenterology. 2015 Nov;149(6):1553-1563.e10. doi: 10.1053/j.gastro.2015.07.004. Epub 2015 Jul 11. Gastroenterology. 2015. PMID: 26170137 Free PMC article.
-
Intestinal stem cells and inflammation.Curr Opin Pharmacol. 2015 Dec;25:62-6. doi: 10.1016/j.coph.2015.11.008. Epub 2015 Dec 2. Curr Opin Pharmacol. 2015. PMID: 26654865 Review.
-
Wnt signaling, lgr5, and stem cells in the intestine and skin.Am J Pathol. 2009 Mar;174(3):715-21. doi: 10.2353/ajpath.2009.080758. Epub 2009 Feb 5. Am J Pathol. 2009. PMID: 19197002 Free PMC article. Review.
Cited by
-
Azoxymethane-induced carcinogenesis-like model of mouse intestine and mouse embryonic stem cell-derived intestinal organoids.Mol Biol Rep. 2024 Jun 1;51(1):704. doi: 10.1007/s11033-024-09660-w. Mol Biol Rep. 2024. PMID: 38824233
-
Host-microbiota interaction in intestinal stem cell homeostasis.Gut Microbes. 2024 Jan-Dec;16(1):2353399. doi: 10.1080/19490976.2024.2353399. Epub 2024 May 17. Gut Microbes. 2024. PMID: 38757687 Free PMC article. Review.
-
The Potential Reversible Transition between Stem Cells and Transient-Amplifying Cells: The Limbal Epithelial Stem Cell Perspective.Cells. 2024 Apr 25;13(9):748. doi: 10.3390/cells13090748. Cells. 2024. PMID: 38727284 Free PMC article. Review.
-
Nrf-2 as a novel target in radiation induced lung injury.Heliyon. 2024 Apr 10;10(8):e29492. doi: 10.1016/j.heliyon.2024.e29492. eCollection 2024 Apr 30. Heliyon. 2024. PMID: 38665580 Free PMC article. Review.
-
Cellular plasticity and fate determination in gastric carcinogenesis.iScience. 2024 Mar 8;27(4):109465. doi: 10.1016/j.isci.2024.109465. eCollection 2024 Apr 19. iScience. 2024. PMID: 38550991 Free PMC article. Review.
References
-
- Barker N, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003–1007. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases