How is the transition of intestinal stem cells from fetal to adult controlled?

The process by which organs are formed, passing from an immature state to a fully mature and functional one, is extremely complex and largely unknown. There are still many cellular and molecular mechanisms that control the process about which almost nothing is known. In the case of the intestine, this implies acquiring the capacity to digest and absorb nutrients, a process controlled molecularly by specific transcription factors. These transcription factors are responsible for turning genes that code for proteins that allow cells to transition between fetal or adult stem cells and differentiated cells on and off.

Deciphering the functioning of certain transcription factors in the formation of the intestine has been the objective of the team led by Kim Bak Jensen, from the Center for Stem Cell Medicine of the Novo Nordisk Foundation (reNEW) in Denmark, in which Dr. Jordi Guiu, head of the Cellular Plasticity and Regeneration research group at the Bellvitge Biomedical Research Institute (IDIBELL) and the Clinical Translation Program for Regenerative Medicine of Catalonia (P-CMR)[C]).

This research work has been channeled through two studies whose results have recently been made public.

In the two published studies, the scientific team uses the intestine organoid as a model, a three-dimensional structure similar to mini-intestines created in the laboratory from stem cells. Using different molecular approaches, the usefulness of organoid models to identify the factors that regulate cell fate is demonstrated, and it is revealed that the transcription factors SMARCA4 and SMARCC1 prevent early differentiation of stem cells during development. intestinal. In addition, the transcriptional activity of the YAP protein is identified as the main regulator of the immature fetal state.

The two new studies provide insightful new data on how the transition of intestinal stem cells from fetal to adult is controlled. (Image: Novo Nordisk Foundation Center for Stem Cell Medicine)

Dr. Jordi Guiu explains: “Understanding the transition from an immature organ to a mature organ could help us understand how we can train cells grown in the laboratory to go through different stages of maturity. This knowledge would ultimately help generate cell therapies, for example, by producing epithelial cells in the laboratory that could be transplanted into patients with intestinal ulcers such as Chron’s disease, or patients treated with cavity radiotherapy. abdomen, among other epithelial defects”.

One of the studies is titled “Transcriptional and epigenomic profiling identifies YAP signaling as a key regulator of intestinal epithelium maturation” and its first author is Laura M. Pikkupeura, from the University of Copenhagen in Denmark.

The other study is titled “An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell” and its first author is Stine L. Hansen, from the Novo Nordisk Foundation Center for Stem Cell Medicine in Denmark.

Both studies have been published in the academic journal Science Advances. (Source: IDIBELL)