Tuft cells act as regenerative stem cells in the human intestine

Lulu Huang, Jochem H. Bernink*, Amir Giladi, Daniel Krueger, Gijs J.F. van Son, Maarten H. Geurts, Georg Busslinger, Lin Lin, Harry Begthel, Maurice Zandvliet, Christianne J. Buskens, Willem A. Bemelman, Carmen López-Iglesias, Peter J. Peters, Hans Clevers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 (ref. 1). 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 mice2–4. This occurs through proliferation of pre-existing tuft cells, rather than through increased de novo generation from stem cells. Indeed, proliferative tuft cells occur in vivo both in fetal and in adult human intestine. Single mature proliferating tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans.
Original languageEnglish
Pages (from-to)929-935
Number of pages7
JournalNature
Volume634
Issue number8035
Early online date1 Jan 2024
DOIs
Publication statusPublished - 24 Oct 2024

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