Biochemical controls: gut stem cell development (Introduction)

by David Turell @, Saturday, August 19, 2023, 16:15 (299 days ago) @ David Turell

Type established first then migration:

"These discoveries were made using intestinal organoids and the new TypeTracker technique, which can now be used to understand other organs at the cellular level and the effects of mutations and medications.


"Our intestines contain different types of cells, each of which has a specific task. Just like in many other places in our body, the cells in the intestines are constantly renewed: stem cells develop into specialized cells that perform a function, for example, to secrete substances that protect the intestine or to absorb nutrients from food.

"'From previous research we know that stem cells reside in the valleys of the intestinal wall (the 'crypts'), while most specialized and functional cells are located at the top of the mountains (the 'villi')," say Sander Tans and Jeroen van Zon, who directed the research jointly at AMOLF.

"'The cells in the intestinal wall are renewed about every week, using the stem cells in the crypts that grow, divide and migrate to the villi. We used to think that by moving upwards to the villus, the stem cells are instructed to become a functional cell. This has been a very appealing model, as it naturally explains how these functional cells are positioned at the right location. However, our data shows a different picture."


"This new type of data showed that stem cells adopted their functional identity much earlier than previously thought. They did so when still deep inside the crypt, before migrating towards the villus region that was thought to provide the trigger to start the specialization process.


"'Various medical conditions are thought to be caused by an imbalance between cell types. For instance those that secrete hormones, which has been linked to intestinal bowel syndrome (IBS), the sensation of fullness, but also the so-called gut-brain axis.

"'Understanding how cells choose their identity is key to uncovering the regulation of this balance, and to controlling it through medical interventions. Furthermore, if we want to better understand which molecular signals underpin the fate choices, we need to look into the earlier stages, when cells still have a strong stem identity and other known molecular signals, such as the WNT pathway that plays a role in cell specialization, are still high."

"The equipment and procedure for the TypeTracker method is relatively simple. Therefore, it is also promising for all types of other research on organoids. "Cell identity is central to all organ functions, and was previously only known in static pictures. This method allows one to look at the dynamics at the cellular level. One can for instance investigate whether the same commit-then-sort principle holds for other organs with a completely different three-dimensional structure, such as breast tissue that consists of channels," says Zheng."

comment: I wonder if this principal applies to all aspects of stem cells in embryology.

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