Cargando…
Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members
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 th...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481656/ https://www.ncbi.nlm.nih.gov/pubmed/37493498 http://dx.doi.org/10.15252/embr.202256454 |
_version_ | 1785102025363554304 |
---|---|
author | Berková, Linda Fazilaty, Hassan Yang, Qiutan Kubovčiak, Jan Stastna, Monika Hrckulak, Dusan Vojtechova, Martina Dalessi, Tosca Brügger, Michael David Hausmann, George Liberali, Prisca Korinek, Vladimir Basler, Konrad Valenta, Tomas |
author_facet | Berková, Linda Fazilaty, Hassan Yang, Qiutan Kubovčiak, Jan Stastna, Monika Hrckulak, Dusan Vojtechova, Martina Dalessi, Tosca Brügger, Michael David Hausmann, George Liberali, Prisca Korinek, Vladimir Basler, Konrad Valenta, Tomas |
author_sort | Berková, Linda |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10481656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104816562023-09-07 Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members Berková, Linda Fazilaty, Hassan Yang, Qiutan Kubovčiak, Jan Stastna, Monika Hrckulak, Dusan Vojtechova, Martina Dalessi, Tosca Brügger, Michael David Hausmann, George Liberali, Prisca Korinek, Vladimir Basler, Konrad Valenta, Tomas EMBO Rep Articles 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. John Wiley and Sons Inc. 2023-07-26 /pmc/articles/PMC10481656/ /pubmed/37493498 http://dx.doi.org/10.15252/embr.202256454 Text en © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Berková, Linda Fazilaty, Hassan Yang, Qiutan Kubovčiak, Jan Stastna, Monika Hrckulak, Dusan Vojtechova, Martina Dalessi, Tosca Brügger, Michael David Hausmann, George Liberali, Prisca Korinek, Vladimir Basler, Konrad Valenta, Tomas Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members |
title | Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members |
title_full | Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members |
title_fullStr | Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members |
title_full_unstemmed | Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members |
title_short | Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members |
title_sort | terminal differentiation of villus tip enterocytes is governed by distinct tgfβ superfamily members |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481656/ https://www.ncbi.nlm.nih.gov/pubmed/37493498 http://dx.doi.org/10.15252/embr.202256454 |
work_keys_str_mv | AT berkovalinda terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT fazilatyhassan terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT yangqiutan terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT kubovciakjan terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT stastnamonika terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT hrckulakdusan terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT vojtechovamartina terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT dalessitosca terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT bruggermichaeldavid terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT hausmanngeorge terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT liberaliprisca terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT korinekvladimir terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT baslerkonrad terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers AT valentatomas terminaldifferentiationofvillustipenterocytesisgovernedbydistincttgfbsuperfamilymembers |