In an article in Nature , Hubrecht Institute researchers describe how stem cells in the intestine are preserved. This helps our understanding of intestinal diseases.
In the 28 November number of Nature (advance online publication), Prof. Hans Clevers and his colleagues at the Hubrecht Institute describe how "Paneth cells" play a key role in preserving stem cells in the intestine. It was already known that these cells produce antibacterial substances and thus protect the stem cells. Paneth cells, however, are extremely special "bodyguards". They not only protect the stem cells but if they were not there the stem cells could not even exist.
Researchers at the Hubrecht Institute discovered the stem cells – which are recognisable by the presence of the protein Lgr5 on their surface – in the intestine several years ago. The researchers have used the stem cells to grow "mini intestines" outside the body. The question that needed to be answered was how they succeed in retaining their identity. Intestinal stem cells divide continuously and about half of their progeny develop into normal intestinal cells. However, enough stem cells need to survive. Prof. Clevers and his colleagues demonstrate in their article in Nature that the Paneth cells make this possible. These special intestinal cells are close to the stem cells.
Paneth cells create a special environment – a kind of "niche" – where stem cells are produced and survive. They produce signalling substances (Wnt, EGF, Notch ligand) that stem cells require if they are to survive. Mice without Paneth cells also turn out to have very few stem cells in their intestine and when stem cells lose contact with Paneth cells, they lose their "stem cell power". The Paneth cells in fact develop from the stem cells that they themselves preserve and protect. This means that stem cells create their own niche.
The results are interesting not just from the point of view of biology but they also help understand some intestinal disorders. In patients with chronic inflammatory bowel disease (IBD), for example, the Paneth cells do not appear to be functioning properly. Mutations in the Wnt protein also play a major role in cancer of the large intestine, as was already shown in previous research by Prof. Clevers. The recent study suggests that these mutations mean that stem cells become uncoupled, as it were, from the controlling Paneth cells, thus allowing them to divide out of control.
The Hubrecht Institute is an Academy institute and is affiliated to Utrecht University Medical Centre. (UMC).
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