Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway

Abstract Mitochondrial gene expression is pivotal to cell metabolism. Nevertheless, it is unknown whether it diverges within a given cell type. Here, we analysed single-cell RNA-seq experiments from human pancreatic alpha (N = 3471) and beta cells (N = 1989), as well as mouse beta cells (N = 1094)....

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Autores principales:	H. Medini, T. Cohen, D. Mishmar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/52e5b80514164c798de17cdea8a010dd
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spelling	oai:doaj.org-article:52e5b80514164c798de17cdea8a010dd2021-12-02T15:23:10ZMitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway10.1038/s41598-020-80334-w2045-2322https://doaj.org/article/52e5b80514164c798de17cdea8a010dd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80334-whttps://doaj.org/toc/2045-2322Abstract Mitochondrial gene expression is pivotal to cell metabolism. Nevertheless, it is unknown whether it diverges within a given cell type. Here, we analysed single-cell RNA-seq experiments from human pancreatic alpha (N = 3471) and beta cells (N = 1989), as well as mouse beta cells (N = 1094). Cluster analysis revealed two distinct human beta cells populations, which diverged by mitochondrial (mtDNA) and nuclear DNA (nDNA)-encoded oxidative phosphorylation (OXPHOS) gene expression in healthy and diabetic individuals, and in newborn but not in adult mice. Insulin gene expression was elevated in beta cells with higher mtDNA gene expression in humans and in young mice. Such human beta cell populations also diverged in mitochondrial RNA mutational repertoire, and in their selective signature, thus implying the existence of two previously overlooked distinct and conserved beta cell populations. While applying our approach to human alpha cells, two sub-populations of cells were identified which diverged in mtDNA gene expression, yet these cellular populations did not consistently diverge in nDNA OXPHOS genes expression, nor did they correlate with the expression of glucagon, the hallmark of alpha cells. Thus, pancreatic beta cells within an individual are divided into distinct groups with unique metabolic-mitochondrial signature.H. MediniT. CohenD. MishmarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q H. Medini T. Cohen D. Mishmar Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
description	Abstract Mitochondrial gene expression is pivotal to cell metabolism. Nevertheless, it is unknown whether it diverges within a given cell type. Here, we analysed single-cell RNA-seq experiments from human pancreatic alpha (N = 3471) and beta cells (N = 1989), as well as mouse beta cells (N = 1094). Cluster analysis revealed two distinct human beta cells populations, which diverged by mitochondrial (mtDNA) and nuclear DNA (nDNA)-encoded oxidative phosphorylation (OXPHOS) gene expression in healthy and diabetic individuals, and in newborn but not in adult mice. Insulin gene expression was elevated in beta cells with higher mtDNA gene expression in humans and in young mice. Such human beta cell populations also diverged in mitochondrial RNA mutational repertoire, and in their selective signature, thus implying the existence of two previously overlooked distinct and conserved beta cell populations. While applying our approach to human alpha cells, two sub-populations of cells were identified which diverged in mtDNA gene expression, yet these cellular populations did not consistently diverge in nDNA OXPHOS genes expression, nor did they correlate with the expression of glucagon, the hallmark of alpha cells. Thus, pancreatic beta cells within an individual are divided into distinct groups with unique metabolic-mitochondrial signature.
format	article
author	H. Medini T. Cohen D. Mishmar
author_facet	H. Medini T. Cohen D. Mishmar
author_sort	H. Medini
title	Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
title_short	Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
title_full	Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
title_fullStr	Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
title_full_unstemmed	Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
title_sort	mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/52e5b80514164c798de17cdea8a010dd
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Mitochondrial gene expression in single cells shape pancreatic beta cells' sub-populations and explain variation in insulin pathway

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