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It's all about the (stem cell) neighborhood

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Stem cells have the ability to develop, or differentiate, into the many different cell types in the body. They also serve as a repair system to replace aged or damaged cells. With their regenerative abilities, stem cells offer enormous potential in treating many diseases.

Researchers at Duke-NUS Medical School have now identified how the stem cell neighborhood keeps stem cells in the gut alive.

Stems cells in our adult tissues live in very specific locations called stem cell niches. These niches provide a specialized, ideal neighborhood for stem cells. The stem cells in the niche are undifferentiated, meaning they have not yet changed into a mature cell. The niche regulates how stem cells participate in tissue generation, maintenance and repair. The niche prevents stem cells from being depleted, while protecting the body from over-production of stem cells. Understanding stem cell niches is therefore important in the field of stem cell therapeutics.

Understanding the role of the niche requires identifying the key cell types that regulate the numerous processes that take place within the niche. In the intestinal stem cell niche, the key regulators are hormones called R-spondins and Wnts, which are frequently expressed together. However, it is still unclear what type of niche cells make the Wnts and R-spondins.

A team headed by visiting scientist Gedas Greicius, Ph.D., and David Virshup, M.D., director of the cancer and stem cell biology program at Duke-NUS Medical School, studied the source and functional role of Wnts and RSPO3. RSPO3 is by far the most abundant R-spondin produced in the mouse small intestine.

Using a mouse model, the team identified a specific cell called a subepithelial myofibroblast as an essential source of both Wnts and RSPO3. If these niche cells cannot make Wnts, mice do not develop adult intestines, and if these niche cells cannot make RSPO3, mice cannot repair the intestine after injury. Their work demonstrates the close interaction between epithelial stem cells and the niche that regulates them.

This research provides new insights into the structure of the stem cell niche in health and after injury.

Stromal RSPO3 and Wnts are critical for adult intestinal homeostasis. Image courtesy of Duke-NUS Medical School.

Learn more:

https://www.eurekalert.org/pub_releases/2018-04/dms-iaa040518.php

DOI: 10.1073/pnas.1713510115