Researchers uncover drivers of healthy gut maintenance

Date:
June 15, 2020
Source:
The Francis Crick Institute
Summary:
Researchers have found two genes that regulate the differentiation
of stem cells in the small intestine, offering valuable insight
into how the body develops and maintains a healthy gut.



FULL STORY ========================================================================== Researchers at the Francis Crick Institute have found two genes that
regulate the differentiation of stem cells in the small intestine,
offering valuable insight into how the body develops and maintains a
healthy gut.


========================================================================== Cells in the lining of the small intestine are replaced around every five
days, the quickest rate for any organ in the body. This fast replacement
helps the lining cope with the damage it suffers as a result of breaking
down food and absorbing nutrients.

This process, which is important for the healthy functioning of the
small intestine, is supported by the stem cells in a part of the small intestine called the crypt.

In their study, published in Gastroenterology, the researchers found
two genes, MTG8 and MTG16, which are highly expressed in cells that have
just left the stem cell zone. These genes 'switch off' signals that keep
these cells in a multipotent or 'immature' state, leading them to start
to differentiate.

When the team analysed intestinal tissue and small intestine organoids
grown from mice lacking these genes, they found there were many more
stem cells, indicating that the process of differentiation was impeded.

Anna Baulies, lead author and postdoctoral training fellow in the Stem
Cell and Cancer Biology lab at the Crick says: "These genes maintain the
flow of cells which are needed for the healthy functioning of the small intestine, starting the stem cells on the road to become enterocyte
cells which are needed to absorb nutrients." Importantly, by working
with human small intestine organoids, the researchers also found that
while the stem cells are still in the crypt, these genes are repressed
by a key developmental pathway, Notch signalling. This ensures the stem
cells do not differentiate too early.

Vivian Li, senior author and group leader of the Stem Cell and Cancer
Biology lab at the Crick says, "Understanding the role these genes play
in healthy tissue will also help us to understand how the intestine
regularly regenerates and also if these genes are a helpful or harmful
force in the presence of disease." "For example, loss of these genes
may increase the number of stem cells and contribute to colorectal
cancer progression. Further study on the underlying mechanism might be
helpful to limit the number of stem cells in the cancer." The signal
that these genes repress, Wnt signalling, also keeps stem cells in a multipotent state in many other tissues, including the skin, stomach,
liver and brain. These findings could therefore help other research into
stem cell differentiation outside of the small intestine.

The researchers will continue this work, looking to understand more about
the mechanism these two genes use to regulate stem cell differentiation
and regeneration.


========================================================================== Story Source: Materials provided by The_Francis_Crick_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Anna Baulies, Nikolaos Angelis, Valentina Foglizzo, E. Thomas
Danielsen,
Harshil Patel, Laura Novellasdemunt, Anna Kucharska, Joana Carvalho,
Emma Nye, Paolo De Coppi, Vivian S.W. Li. The Transcription
co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells
From Their Niche and Differentiation into Enterocyte vs Secretory
Lineages. Gastroenterology, 2020; DOI: 10.1053/j.gastro.2020.06.012 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200615140821.htm

--- up 20 weeks, 6 days, 2 hours, 34 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)