Scientific article
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English

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

Published inNature Communications, vol. 12, no. 1, 4458
Publication date2021
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
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Cell Lineage / genetics
  • Female
  • Gene Knock-In Techniques
  • Humans
  • Insulin / biosynthesis
  • Insulin-Secreting Cells / classification
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Pancreas / cytology
  • Pancreas / embryology
  • Pancreas / growth & development
  • Pancreatic Polypeptide / deficiency
  • Pancreatic Polypeptide / genetics
  • Pancreatic Polypeptide / metabolism
  • Pancreatic Polypeptide-Secreting Cells / classification
  • Pancreatic Polypeptide-Secreting Cells / cytology
  • Pancreatic Polypeptide-Secreting Cells / metabolism
  • Pregnancy
  • Protein Precursors / metabolism
  • RNA-Seq
Funding
  • Autre - This work was funded with grants from Swiss National Science Foundation, European Research Council, and Fondation Aclon to P.L.H
Citation (ISO format)
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
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Article (Published version)
Secondary files (2)
Identifiers
ISSN of the journal2041-1723
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122downloads

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Creation07/26/2021 3:41:00 PM
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