2016-02-16 15:25:43 UTC

CMGH Research Identifies Non-Epithelial Cell that Maintains Intestinal Epithelial Stem Cell Niche

Feb. 16, 2016

Targeting the function of niche cells may be critical in re-establishing normal mucosal integrity in various GI diseases.

A newly accepted article-in-press in Cellular and Molecular Gastroenterology and Hepatology (CMGH) is viewed as a major breakthrough in stem cell biology. The article, “Foxl1-Expressing Mesenchymal Cells Constitute the Intestinal Stem Cell Niche,” by Klaus H. Kaestner, PhD, and colleagues, provides insight into the fundamental niche for intestinal stem cells.

The concept of a critical “niche” in each intestinal crypt unit suggests that local intrinsic properties promote and maintain the stem cells and their division and differentiation to produce each of the epithelial cell types normally found within the mucosa.

Previous studies have suggested that Paneth cells were responsible for generating this niche and, perhaps, that Paneth-like cells serve this function in the left colon where Paneth cells are not normally present. However, ablation of Paneth cells has not impaired mucosal integrity. The new study by Kaestner and colleagues now demonstrates that non-epithelial, mesenchymal cells, which can be recognized by their expression of the transcription factor Foxl1, create the stem cell niche. These Foxl1-expressing cells cup the bottom of each crypt unit and likely provide the growth factors necessary for maintenance of the unique environment. This is somewhat surprising, as it indicates that the critical coordinator of epithelial homeostasis is not an epithelial cell, but rather a population of stromal cells that surround the crypt.

This work has major implications, as it is likely that many intestinal disorders — including celiac disease and inflammatory bowel disease — may benefit from increased stem cell proliferation to promote mucosal healing. Future research will need to focus on how Foxl1-expressing niche cells communicate with the epithelial stem cells to produce the appropriate numbers and types of epithelial cells.

Read the full open-access study on the CMGH website.

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