Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members

0575880 - ÚMG 2024 RIV US eng J - Journal Article
Berková, Linda - Fazilaty, H. - Yang, Q. - Kubovčiak, Jan - Šťastná, Monika - Hrčkulák, Dušan - Vojtěchová, Martina - Dalessi, T. - Brügger, M. D. - Hausmann, G. - Liberali, P. - Kořínek, Vladimír - Basler, K. - Valenta, Tomáš
Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members.
Embo Reports. Roč. 24, č. 9 (2023), č. článku e56454. ISSN 1469-221X. E-ISSN 1469-3178
R&D Projects: GA ČR GA21-26025S; GA MŠMT LX22NPO5102
Institutional support: RVO:68378050
Keywords : enterocytes * epithelial differentiation * intestinal mesenchymal cells * small intestine * Tgfβ / Bmp signalling
OECD category: Cell biology
Impact factor: 7.7, year: 2022
Method of publishing: Open access
https://www.embopress.org/doi/full/10.15252/embr.202256454

The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed from the centre to the upper part of the villus and activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus tip mesenchymal cells and it influences the adhesive properties of villus tip epithelial cells and the expression of immunomodulators. Additionally, Tgfβ induces epithelial gene expression programs similar to those triggered by Bmp2. Bmp2-driven villus tip program is activated by a canonical Bmp receptor type I/Smad-dependent mechanism. Finally, we establish an organoid cultivation system that enriches villus tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Our data suggest that not only a Bmp gradient but also the activity of individual Bmp drives specific enterocytic programs.
Permanent Link: https://hdl.handle.net/11104/0345587