Tufted cells act as regenerative stem cells in human gut, study finds

Cells in intestinal tufts divide to produce new cells when immunological signals trigger them. Furthermore, unlike progenitor and stem cells, tuft cells can survive severe injuries such as irradiation damage and contribute to epithelial regeneration. This is what researchers from the Organoid group at the Hubrecht Institute discovered using miniature human intestines grown in the laboratory.

The results, published in Nature on October 2, 2024, could have important implications for the regeneration of intestinal tissue after injury.

The human intestinal tract is responsible for nutrient absorption and hormone production. In addition, it protects the intestine from pathogens. These important functions are carried out by specialized cells in the epithelium, the tissue that lines the intestines. The epithelium is made up of different types of specialized epithelial cells, including tufted cells.

Tuft cells are found throughout the intestinal tract as well as many other organs. Most of the knowledge about the function and ontology of these cells comes from research in mice. Studies show that a specific category of clump cells protects the intestine from pathogens. When tuft cells detect the presence of pathogens, they signal immune cells and the epithelium to mount a strong defense response. However, due to the lack of human research models, the function of clump cells in the human intestinal tract had remained unknown.

This was more than enough reason for researchers from the Organoid group to explore this question further using the unique organoid technology they developed. They grew miniature intestines in a dish, which mimic the function of real human intestines. The structures, called organoids, contain all the different types of intestinal cells.

Lulu Huang, co-first author of the paper with Jochem Bernink and Amir Giladi, explains: “We used these organoids to carefully monitor the development and function of the tuft cells. function of organoids.

Tufted cells act as reserve stem cells

One of the most important discoveries made by researchers is that clump cells can proliferate when immunological signals trigger them.

“Upon receiving such immunological signals, tuft cells divide to produce new tuft cells, which can in turn transdifferentiate and generate all other epithelial cell types. Through this process, tuft cells can restore the injured intestine,” Bernink explains.

What’s particularly impressive about clump cells is that they survive damage from irradiation. Where stem and progenitor cells lose their ability to proliferate after such damage, tuft cells can survive and generate all different types of intestinal epithelial cells.

Huang notes: “We also grew organoids without clump cells, and these organoids were unable to recover from radiation damage. » Tufted cells therefore play an essential role in repairing intestinal tissue in the event of damage.

“Tufted cells essentially form a pool of reserve stem cells in the human intestine, a pool that springs into action in the event of damage,” explains Bernink. The findings could have implications for regenerative medicine, an area of ​​research focused on tissue repair and restoration.

“In addition to further research into the exact regenerative function of human tuft cells, it would be interesting to study the function of tuft cells in other organs, for example in the liver, urinary tract and lungs,” concludes Huang.