Since the discovery of LGR5 as a marker of intestinal stem cells, we have learned a great deal about the intestinal crypt stem cell niche. In the August issue of Gastroenterology Bon-Kyoung Koo and Hans Clevers review the discovery of crypt base columnar cells as LGR5+ adult stem cells and summarize the progress and challenges of the field of intestinal stem cell research.
The intestinal epithelium renews every 3−5 days in adults. This rapid turnover is sustained by tissue-specific stem cells located in crypts. These cells divide every 24 hrs, generating rapidly proliferative progenitors that fill the pocket-like crypts (see figure).
There are several markers of intestinal stem cells. Koo and Clevers review the function and significance of LGR5, the product of a locus regulated by WNT, as a marker of these crypt base columnar cells.
Although LGR5 is a marker of intestinal stem cells, Koo and Clevers explain that it is expressed in a small number of cells in many tissues. Rapidly dividing, long-lived LGR5+ adult stem cells have been detected in hair follicles, the stomach pylorus, and the colon.
LGRs are receptors for R-spondins (RSPOs)—agonists of the WNT pathway. Koo and Clevers discuss how LGR4, 5, and 6 promote WNT signaling upon their association with RSPO, and the genes that regulate intestinal stem cell activites.
The authors explain how the study of stem cell–enriched genes has led to new information about the WNT signaling pathway, and LGR5+ stem cells can be cultured over long periods in vitro as epithelial organoids or mini-guts.
Cultured adult stem cells can now be used in drug development, disease modeling, gene therapy, and regenerative medicine.