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Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production

Cigliola, Valentina
Furuyama, Kenichiro
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Published in Nature communications. 2021, vol. 12, no. 1, 4458
Abstract The cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using different approaches, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon β-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.
Keywords AnimalsBlood Glucose / metabolismBody WeightCell Lineage / geneticsFemaleGene Knock-In TechniquesHumansInsulin / biosynthesisInsulin-Secreting Cells / classificationInsulin-Secreting Cells / cytologyInsulin-Secreting Cells / metabolismMaleMiceMice, TransgenicPancreas / cytologyPancreas / embryologyPancreas / growth & developmentPancreatic Polypeptide / deficiencyPancreatic Polypeptide / geneticsPancreatic Polypeptide / metabolismPancreatic Polypeptide-Secreting Cells / classificationPancreatic Polypeptide-Secreting Cells / cytologyPancreatic Polypeptide-Secreting Cells / metabolismPregnancyProtein Precursors / metabolismRNA-Seq
PMID: 34294685
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
Autre: This work was funded with grants from Swiss National Science Foundation, European Research Council, and Fondation Aclon to P.L.H
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PEREZ FRANCES, Marta et al. Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production. In: Nature Communications, 2021, vol. 12, n° 1, p. 4458. doi: 10.1038/s41467-021-24788-0 https://archive-ouverte.unige.ch/unige:153672

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Deposited on : 2021-08-03

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