Sammanfattning
Enteroendocrine cells (EECs) differentiate and mature to form functionally distinct populations upon migration along the intestinal crypt-villus axis, but how niche signals affect this process is poorly understood. Here, we identify expression of Glial cell line-derived neurotrophic factor (GDNF) in the intestinal subepithelial myofibroblasts (SEMFs), while the GDNF receptor RET was expressed in a subset of EECs, suggesting GDNF-mediated regulation. Indeed, GDNF-RET signaling induced increased expression of EEC genes including Tph1, encoding for the rate-limiting enzyme for 5-hydroxytryptamine (5-HT, serotonin) biosynthesis, and increased the frequency of 5-HT+ enterochromaffin cells (ECs) in mouse organoid culture experiments and in vivo. Moreover, expression of the 5-HT receptor Htr4 was enriched in Lgr5+ intestinal stem cells (ISCs) and 5-HT reduced the ISC clonogenicity. In summary, our results show that GDNF-RET signaling regulate EEC differentiation, and suggest 5-HT as a potential niche factor regulating Lgr5+ ISC activity, with potential implications in intestinal regeneration.
Originalspråk | engelska |
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Artikelnummer | 111246 |
Tidskrift | iScience |
Volym | 27 |
Nummer | 12 |
Antal sidor | 21 |
ISSN | 2589-0042 |
DOI | |
Status | Publicerad - 20 dec. 2024 |
MoE-publikationstyp | A1 Tidskriftsartikel-refererad |
Bibliografisk information
Publisher Copyright:© 2024 The Author(s)
Vetenskapsgrenar
- 1184 Genetik, utvecklingsbiologi, fysiologi
- 1182 Biokemi, cell- och molekylärbiologi