Hebrew University researchers have identified four distinct populations of mesenchymal cells beneath the intestinal lining in mice. Each population is located in a different region and produces a different combination of signals related to stem cells, immunity, tissue structure, and nutrient sensing.
The lining of thebowel It is one of the most rapidly regenerating tissues in the body. It replaces a significant portion of its cells within a few days, in a process that begins withStem cells Housed in tiny pockets called crypts, the new cells move from the crypts toward the villi – the finger-like protrusions that face the intestinal cavity – differentiate and eventually fall off.
A new study by researchers fromThe Hebrew University And from the medical center Hadassah reveals that behind the rapid regeneration is a more complex support system than previously thought. The researchers identified four distinct populations of mesenchymal cells From a dynasty Foxl1, each of which is located in a different area along the axis between the crypt and the tip of the cistern.
The study, led by doctoral student Amal Garbi and Dr. Michal Shushaks-Carmel from the Hebrew University School of Medicine, was published in the journal Cellular and Molecular Gastroenterology and Hepatology.
Not a single population, but a network of specialized cells
Foxl1 lineage cells form a thin network beneath the epithelium—the layer of cells that lines the gut. Previous studies have shown that they provide signals essential for the existence and activity of stem cells in the gut, but they have largely been viewed as a single population.
through Single-cell RNA sequencingUsing in situ hybridization, immunofluorescence staining, and mouse models, the researchers mapped the gene expression in these cells and their location in the tissue. The mapping revealed four distinct populations: cells surrounding the crypt, cells at the base of the crypt, cells in its middle, and cells near its edge.
Each population runs a different genetic program and produces a different combination of signaling molecules. The result is a spatial division of labor: instead of a single supporting cell performing multiple roles, different regions of the intestine create local environments that direct the activity of neighboring cells.
Different signals come from four areas
The cells adjacent to the crypts were rich in signals from the Wnt and R-spondin families, which promote stem cell activity and renewal. They also expressed genes related to the extracellular matrix and the complement system of the immune system.
The cells at the base of the follicle expressed genes related to contraction and mechanical organization of the tissue. The researchers speculate that they may participate in maintaining the structure of the follicles.
In the middle of the cluster, genetic signatures related to immune control and inflammation were found. At the end of the cluster, pathways related to nutrient sensing and the regulation of RNA and protein assemblies stood out.
The division into four populations is not just a difference in location. It points to a hierarchical signaling network that helps coordinate stem cell proliferation in the crypt, cell differentiation on their way up, maintenance of tissue structure, and the local immune response.
Cellular atlas, not yet a treatment
The findings provide a detailed atlas of Foxl1 cells along the crypt-cis axis and may aid in the study of conditions in which the intestinal regeneration and repair mechanisms are disrupted, including mucosal injury andInflammatory bowel disease.
However, the study was conducted in mouse models, and some of the proposed roles are based at this point on the location of the cells and their gene expression signatures. It does not present a new treatment in humans.
The next step will be to examine the role of each of the four populations separately, for example by selectively inactivating them or altering their activity in experimental models. This will allow us to examine which of them are essential for epithelial regeneration, stem cell support, immune activity, and tissue repair after injury.
More on the subject on the science website
- The ARTS protein is responsible for critical processes in intestinal diseases
- The secret is in the texture: Changes in intercellular texture may predict inflammatory bowel disease
- No smoke without inflammation: A new control mechanism in inflammatory bowel diseases
- Helping the body to help itself: how to relieve Crohn's and colitis?
- Without fasting or anesthesia: A noninvasive method for diagnosing inflammatory bowel disease
Questions and Answers
What did the researchers discover?
They identified four distinct populations of Foxl1 lineage supporting cells, located in different regions along the crypts and cisterns in the intestine.
What is the role of supporting cells?
They produce signals that affect stem cells, mucosal regeneration, intestinal structure, and local immune system activity.
How was the research conducted?
The researchers combined single-cell RNA sequencing, imaging methods, and molecular mapping in mouse models.
Does the discovery already make it possible to treat intestinal diseases?
No. This is basic research that provides a new map of cell populations. Further research is needed to clarify their role and the relevance of the findings to humans.
For the scientific article: Opening the scientific article
