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The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent

The transcription factor Stat3 is required for proliferation and pluripotency of embryonic stem cells; we have prepared and characterized fluorescent Stat3-reporter zebrafish based on repeats of minimal responsive elements. These transgenic lines mimic in vivo Stat3 expression patterns and are respo...

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Autores principales: Peron, Margherita, Dinarello, Alberto, Meneghetti, Giacomo, Martorano, Laura, Facchinello, Nicola, Vettori, Andrea, Licciardello, Giorgio, Tiso, Natascia, Argenton, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328161/
https://www.ncbi.nlm.nih.gov/pubmed/32467235
http://dx.doi.org/10.1242/dev.188987
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author Peron, Margherita
Dinarello, Alberto
Meneghetti, Giacomo
Martorano, Laura
Facchinello, Nicola
Vettori, Andrea
Licciardello, Giorgio
Tiso, Natascia
Argenton, Francesco
author_facet Peron, Margherita
Dinarello, Alberto
Meneghetti, Giacomo
Martorano, Laura
Facchinello, Nicola
Vettori, Andrea
Licciardello, Giorgio
Tiso, Natascia
Argenton, Francesco
author_sort Peron, Margherita
collection PubMed
description The transcription factor Stat3 is required for proliferation and pluripotency of embryonic stem cells; we have prepared and characterized fluorescent Stat3-reporter zebrafish based on repeats of minimal responsive elements. These transgenic lines mimic in vivo Stat3 expression patterns and are responsive to exogenous Stat3; notably, fluorescence is inhibited by both stat3 knockout and IL6/Jak/STAT inhibitors. At larval stages, Stat3 reporter activity correlates with proliferating regions of the brain, haematopoietic tissue and intestine. In the adult gut, the reporter is active in sparse proliferating cells, located at the base of intestinal folds, expressing the stemness marker sox9b and having the morphology of mammalian crypt base columnar cells; noteworthy, zebrafish stat3 mutants show defects in intestinal folding. Stat3 reporter activity in the gut is abolished with mutation of T cell factor 4 (Tcf7l2), the intestinal mediator of Wnt/β-catenin-dependent transcription. The Wnt/β-catenin dependence of Stat3 activity in the gut is confirmed by abrupt expansion of Stat3-positive cells in intestinal adenomas of apc heterozygotes. Our findings indicate that Jak/Stat3 signalling is needed for intestinal stem cell maintenance and possibly crucial in controlling Wnt/β-catenin-dependent colorectal cancer cell proliferation.
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spelling pubmed-73281612020-07-10 The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent Peron, Margherita Dinarello, Alberto Meneghetti, Giacomo Martorano, Laura Facchinello, Nicola Vettori, Andrea Licciardello, Giorgio Tiso, Natascia Argenton, Francesco Development Stem Cells and Regeneration The transcription factor Stat3 is required for proliferation and pluripotency of embryonic stem cells; we have prepared and characterized fluorescent Stat3-reporter zebrafish based on repeats of minimal responsive elements. These transgenic lines mimic in vivo Stat3 expression patterns and are responsive to exogenous Stat3; notably, fluorescence is inhibited by both stat3 knockout and IL6/Jak/STAT inhibitors. At larval stages, Stat3 reporter activity correlates with proliferating regions of the brain, haematopoietic tissue and intestine. In the adult gut, the reporter is active in sparse proliferating cells, located at the base of intestinal folds, expressing the stemness marker sox9b and having the morphology of mammalian crypt base columnar cells; noteworthy, zebrafish stat3 mutants show defects in intestinal folding. Stat3 reporter activity in the gut is abolished with mutation of T cell factor 4 (Tcf7l2), the intestinal mediator of Wnt/β-catenin-dependent transcription. The Wnt/β-catenin dependence of Stat3 activity in the gut is confirmed by abrupt expansion of Stat3-positive cells in intestinal adenomas of apc heterozygotes. Our findings indicate that Jak/Stat3 signalling is needed for intestinal stem cell maintenance and possibly crucial in controlling Wnt/β-catenin-dependent colorectal cancer cell proliferation. The Company of Biologists Ltd 2020-06-19 /pmc/articles/PMC7328161/ /pubmed/32467235 http://dx.doi.org/10.1242/dev.188987 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Stem Cells and Regeneration
Peron, Margherita
Dinarello, Alberto
Meneghetti, Giacomo
Martorano, Laura
Facchinello, Nicola
Vettori, Andrea
Licciardello, Giorgio
Tiso, Natascia
Argenton, Francesco
The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent
title The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent
title_full The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent
title_fullStr The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent
title_full_unstemmed The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent
title_short The stem-like Stat3-responsive cells of zebrafish intestine are Wnt/β-catenin dependent
title_sort stem-like stat3-responsive cells of zebrafish intestine are wnt/β-catenin dependent
topic Stem Cells and Regeneration
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328161/
https://www.ncbi.nlm.nih.gov/pubmed/32467235
http://dx.doi.org/10.1242/dev.188987
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