Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.

In the context of type 1 diabetes research and the development of insulin-producing β-cell replacement strategies, whether pancreatic ductal cells retain their developmental capability to adopt an endocrine cell identity remains debated, most likely due to the diversity of models employed to induce...

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Main Authors: Andhira Vieira, Bastien Vergoni, Monica Courtney, Noémie Druelle, Elisabet Gjernes, Biljana Hadzic, Fabio Avolio, Tiziana Napolitano, Sergi Navarro Sanz, Ahmed Mansouri, Patrick Collombat
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6084906?pdf=render
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spelling doaj-466860841aac402fac1d90c508fa37a02020-11-24T20:41:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01138e020153610.1371/journal.pone.0201536Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.Andhira VieiraBastien VergoniMonica CourtneyNoémie DruelleElisabet GjernesBiljana HadzicFabio AvolioTiziana NapolitanoSergi Navarro SanzAhmed MansouriPatrick CollombatIn the context of type 1 diabetes research and the development of insulin-producing β-cell replacement strategies, whether pancreatic ductal cells retain their developmental capability to adopt an endocrine cell identity remains debated, most likely due to the diversity of models employed to induce pancreatic regeneration. In this work, rather than injuring the pancreas, we developed a mouse model allowing the inducible misexpression of the proendocrine gene Neurog3 in ductal cells in vivo. These animals developed a progressive islet hypertrophy attributed to a proportional increase in all endocrine cell populations. Lineage tracing experiments indicated a continuous neo-generation of endocrine cells exhibiting a ductal ontogeny. Interestingly, the resulting supplementary β-like cells were found to be functional. Based on these findings, we suggest that ductal cells could represent a renewable source of new β-like cells and that strategies aiming at controlling the expression of Neurog3, or of its molecular targets/co-factors, may pave new avenues for the improved treatments of diabetes.http://europepmc.org/articles/PMC6084906?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Andhira Vieira
Bastien Vergoni
Monica Courtney
Noémie Druelle
Elisabet Gjernes
Biljana Hadzic
Fabio Avolio
Tiziana Napolitano
Sergi Navarro Sanz
Ahmed Mansouri
Patrick Collombat
spellingShingle Andhira Vieira
Bastien Vergoni
Monica Courtney
Noémie Druelle
Elisabet Gjernes
Biljana Hadzic
Fabio Avolio
Tiziana Napolitano
Sergi Navarro Sanz
Ahmed Mansouri
Patrick Collombat
Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
PLoS ONE
author_facet Andhira Vieira
Bastien Vergoni
Monica Courtney
Noémie Druelle
Elisabet Gjernes
Biljana Hadzic
Fabio Avolio
Tiziana Napolitano
Sergi Navarro Sanz
Ahmed Mansouri
Patrick Collombat
author_sort Andhira Vieira
title Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
title_short Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
title_full Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
title_fullStr Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
title_full_unstemmed Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
title_sort neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
description In the context of type 1 diabetes research and the development of insulin-producing β-cell replacement strategies, whether pancreatic ductal cells retain their developmental capability to adopt an endocrine cell identity remains debated, most likely due to the diversity of models employed to induce pancreatic regeneration. In this work, rather than injuring the pancreas, we developed a mouse model allowing the inducible misexpression of the proendocrine gene Neurog3 in ductal cells in vivo. These animals developed a progressive islet hypertrophy attributed to a proportional increase in all endocrine cell populations. Lineage tracing experiments indicated a continuous neo-generation of endocrine cells exhibiting a ductal ontogeny. Interestingly, the resulting supplementary β-like cells were found to be functional. Based on these findings, we suggest that ductal cells could represent a renewable source of new β-like cells and that strategies aiming at controlling the expression of Neurog3, or of its molecular targets/co-factors, may pave new avenues for the improved treatments of diabetes.
url http://europepmc.org/articles/PMC6084906?pdf=render
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