2025-07-22
Intestinal tuft cell subtypes represent successive stages of maturation driven by crypt-villus signaling gradients
Publication
Publication
Nat. Commun. , Volume 16 - Issue 1 p. 6765 : 1- 18
Intestinal tuft cells are epithelial sentinels that trigger host defense upon detection of parasite-derived compounds. While they represent potent targets for immunomodulatory therapies in inflammation-driven intestinal diseases, their functioning and differentiation are poorly understood. Here, we reveal common intermediary transcriptomes among the previously described tuft-1 and tuft-2 subtypes in mouse and human. Tuft cell subtype-specific reporter knock-ins in organoids show that the two subtypes reflect successive post-mitotic maturation stages within the tuft cell lineage. In vitro stimulation with interleukin-4 and 13 is sufficient to fuel the generation of new Nrep+ tuft-1 cells, arising from tuft precursors (tuft-p). Subsequently, changes in crypt-villus signaling gradients, such as BMP, and cholinergic signaling, are required to advance maturation towards Chat+ tuft-2 phenotypes. Functionally, we find chemosensory capacity to increase during maturation. Our tuft subtype-specific reporters and optimized differentiation strategy in organoids provide a platform to study immune-related tuft cell subtypes and their unique chemosensory properties.
| Additional Metadata | |
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| Springer Science | |
| Netherlands Organisation for Scientific Research (NWO) | |
| doi.org/10.1038/s41467-025-61878-9 | |
| Nat. Commun. | |
| Organisation | Biophysics |
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Buissant des Amorie, J., Betjes, M., Bernink, J., Hageman, J., Geurts, V., Begthel, H., … Snippert, H. (2025). Intestinal tuft cell subtypes represent successive stages of maturation driven by crypt-villus signaling gradients. Nat. Commun., 16(1), 6765 : 1–18. doi:10.1038/s41467-025-61878-9 |
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