Gut instinct: How intestinal stem cells find their niche

Apr 10, 2015 by Stephanie Dutchen New research indicates how and when adult intestinal stem cells (dark pink) set up shop at the base of villi, as shown in this image from the intestine of a chick near hatching. Credit: Tabin lab

Mommy, where do intestinal stem cells come from? All right, it's not likely a kindergartner would ask such a question. But evolutionary biologists want to know.

Adult intestinal stem cells live at the bases of our villi, the tiny, fingerlike protuberances that line the intestines and absorb nutrients.

There, the stem cells constantly churn out new intestinal cells to replace those being destroyed by corrosive digestive juices.

The researchers asked: How and when do these stem cells appear in the right place so they can do their job?

Studying mice and chicks, whose intestinal formation is similar to ours, the team found that the entire intestinal lining has stem cell properties at first. As the embryo develops, all but a few cells lose this potential.

"This lends support to the theory that adult stem cells are remnants of a more general pool of cells in the embryo," said Amy Shyer, who conducted the work as a graduate student in the lab of Cliff Tabin at Harvard Medical School and is now a Miller Fellow at the University of California, Berkeley.

As for why these cells are restricted to the villi bases, or crypts, the researchers believe the structure of the developing intestine determines which cells receive signals from neighboring tissues that say, "Stop being stem cells."

About two weeks into development, the intestine, initially a smooth tube, starts to form mountainous zigzags that will ultimately become villi. Cells at the peaks are exposed to signals that suppress stem cell properties, while cells in the valleys don't receive them.

"This opens a new door conceptually," said Shyer. "Tissues that start out uniform but then need to set up regions with regular patternswhich happens in the gut, skin, lungs and other organs during embryonic developmentmight coopt these natural changes in architecture to dictate signals that specify cell fate locally."

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Gut instinct: How intestinal stem cells find their niche