Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation

Abstract Glucose-induced insulin secretion, a hallmark of mature β-cells, is achieved after birth and is preceded by a phase of intense proliferation. These events occurring in the neonatal period are decisive for establishing an appropriate functional β-cell mass that provides the required insulin...

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Autores principales:	Jonathan Sobel, Claudiane Guay, Ofer Elhanani, Adriana Rodriguez-Trejo, Lisa Stoll, Véronique Menoud, Cécile Jacovetti, Michael D. Walker, Romano Regazzi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b8ebcf5f93ea4a368630185da5395111
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spelling	oai:doaj.org-article:b8ebcf5f93ea4a368630185da53951112021-12-02T16:45:22ZScrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation10.1038/s41598-021-88003-22045-2322https://doaj.org/article/b8ebcf5f93ea4a368630185da53951112021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88003-2https://doaj.org/toc/2045-2322Abstract Glucose-induced insulin secretion, a hallmark of mature β-cells, is achieved after birth and is preceded by a phase of intense proliferation. These events occurring in the neonatal period are decisive for establishing an appropriate functional β-cell mass that provides the required insulin throughout life. However, key regulators of gene expression involved in functional maturation of β-cells remain to be elucidated. Here, we addressed this issue by mapping open chromatin regions in newborn versus adult rat islets using the ATAC-seq assay. We obtained a genome-wide picture of chromatin accessible sites (~ 100,000) among which 20% were differentially accessible during maturation. An enrichment analysis of transcription factor binding sites identified a group of transcription factors that could explain these changes. Among them, Scrt1 was found to act as a transcriptional repressor and to control β-cell proliferation. Interestingly, Scrt1 expression was controlled by the transcriptional repressor RE-1 silencing transcription factor (REST) and was increased in an in vitro reprogramming system of pancreatic exocrine cells to β-like cells. Overall, this study led to the identification of several known and unforeseen key transcriptional events occurring during β-cell maturation. These findings will help defining new strategies to induce the functional maturation of surrogate insulin-producing cells.Jonathan SobelClaudiane GuayOfer ElhananiAdriana Rodriguez-TrejoLisa StollVéronique MenoudCécile JacovettiMichael D. WalkerRomano RegazziNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonathan Sobel Claudiane Guay Ofer Elhanani Adriana Rodriguez-Trejo Lisa Stoll Véronique Menoud Cécile Jacovetti Michael D. Walker Romano Regazzi Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
description	Abstract Glucose-induced insulin secretion, a hallmark of mature β-cells, is achieved after birth and is preceded by a phase of intense proliferation. These events occurring in the neonatal period are decisive for establishing an appropriate functional β-cell mass that provides the required insulin throughout life. However, key regulators of gene expression involved in functional maturation of β-cells remain to be elucidated. Here, we addressed this issue by mapping open chromatin regions in newborn versus adult rat islets using the ATAC-seq assay. We obtained a genome-wide picture of chromatin accessible sites (~ 100,000) among which 20% were differentially accessible during maturation. An enrichment analysis of transcription factor binding sites identified a group of transcription factors that could explain these changes. Among them, Scrt1 was found to act as a transcriptional repressor and to control β-cell proliferation. Interestingly, Scrt1 expression was controlled by the transcriptional repressor RE-1 silencing transcription factor (REST) and was increased in an in vitro reprogramming system of pancreatic exocrine cells to β-like cells. Overall, this study led to the identification of several known and unforeseen key transcriptional events occurring during β-cell maturation. These findings will help defining new strategies to induce the functional maturation of surrogate insulin-producing cells.
format	article
author	Jonathan Sobel Claudiane Guay Ofer Elhanani Adriana Rodriguez-Trejo Lisa Stoll Véronique Menoud Cécile Jacovetti Michael D. Walker Romano Regazzi
author_facet	Jonathan Sobel Claudiane Guay Ofer Elhanani Adriana Rodriguez-Trejo Lisa Stoll Véronique Menoud Cécile Jacovetti Michael D. Walker Romano Regazzi
author_sort	Jonathan Sobel
title	Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
title_short	Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
title_full	Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
title_fullStr	Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
title_full_unstemmed	Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
title_sort	scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b8ebcf5f93ea4a368630185da5395111
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Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation

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