Tuft cells are present throughout the intestinal tract as well as in many organs. Studies in mice have shown that when tuft cells sense the presence of pathogens, they signal to immune cells and to the epithelium to initiate a strong defense response. However, the function of tuft cells in the human intestinal tract remains unknown due to a lack of human research models. Now, using miniature human intestines grown in the lab, researchers at the Hubrecht Institute and collaborators have discovered intestinal tuft cells divide to make new cells when triggered by immunological cues. Additionally, in comparison to progenitor and stem cells, tuft cells can survive severe injury such as irradiation damage, and contribute to the epithelium’s regeneration. The findings suggest tuft cells act as regenerative stem cells in the human intestine.
The new study is published in Nature in an article titled, “Tuft cells act as regenerative stem cells in the human intestine.”
“In mice, intestinal tuft cells have been described as a long-lived, postmitotic cell type. Two distinct subsets have been identified: tuft-1 and tuft-2,” the researchers wrote. “By combining analysis of primary human intestinal resection material and intestinal organoids, we identify four distinct human tuft cell states, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that tuft cell numbers rapidly increase on interleukin-4 (IL-4) and IL-13 exposure, as reported previously in mice.”
The researchers grew miniature intestines in a dish, which mimic the function of actual human intestines. Lulu Huang, co-first author of the paper together with Jochem Bernink, PhD, and Amir Giladi, PhD, explained: “We used these organoids to carefully monitor the development and function of tuft cells. Moreover, this model enabled us to study the effect of radiation on the function of the organoids.”
One of the discoveries the researchers made was that tuft cells can proliferate when immunological cues trigger them. “Upon receiving such immunological signals, tuft cells divide to make new tuft cells, which can in turn transdifferentiate and generate all other epithelial cell types. Through this process, tuft cells can restore the wounded gut,” said Bernink.
“We also grew organoids without tuft cells, and these organoids were unable to recover from radiation damage,” added Huang. Tuft cells, therefore, play an essential role in repairing intestinal tissue upon damage.
“Tuft cells basically form a pool of reserve stem cells in the human intestines. A pool that is brought to action when damage has occurred,” Bernink explained. The findings may have implications for regenerative medicine, a field of research that focuses on the repair and restoration of tissue. “In addition to more 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,” Huang concluded.
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