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Int J Biochem Cell Biol. 2017 Jul;88:226-235. doi: 10.1016/j.biocel.2017.01.008. Epub 2017 Jan 22.

Dnmt1 activity is dispensable in δ-cells but is essential for α-cell homeostasis.

Author information

1
Department of Genetic Medicine & Development, Faculty of Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland; Centre facultaire du diabète, University of Geneva, Geneva, Switzerland.
2
Department of Developmental Biology, Stanford University School of Medicine, CA 94305, United States; Department of Medicine, Stanford, CA 94305, United States.
3
Department of Genetic Medicine & Development, Faculty of Medicine, University of Geneva, 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland; Centre facultaire du diabète, University of Geneva, Geneva, Switzerland. Electronic address: pedro.herrera@unige.ch.

Abstract

In addition to β-cells, pancreatic islets contain α- and δ-cells, which respectively produce glucagon and somatostatin. The reprogramming of these two endocrine cell types into insulin producers, as observed after a massive β-cell ablation in mice, may help restoring a functional β-cell mass in type 1 diabetes. Yet, the spontaneous α-to-β and δ-to-β conversion processes are relatively inefficient in adult animals and the underlying epigenetic mechanisms remain unclear. Several studies indicate that the conserved chromatin modifiers DNA methyltransferase 1 (Dnmt1) and Enhancer of zeste homolog 2 (Ezh2) are important for pancreas development and restrict islet cell plasticity. Here, to investigate the role of these two enzymes in α- and δ-cell development and fate maintenance, we genetically inactivated them in each of these two cell types. We found that loss of Dnmt1 does not enhance the conversion of α- or δ-cells toward a β-like fate. In addition, while Dnmt1 was dispensable for the development of these two cell types, we noticed a gradual loss of α-, but not δ-cells in adult mice. Finally, we found that Ezh2 inactivation does not enhance α-cell plasticity, and, contrary to what is observed in β-cells, does not impair α-cell proliferation. Our results indicate that both Dnmt1 and Ezh2 play distinct roles in the different islet cell types.

KEYWORDS:

Beta-cell regeneration; Dnmt1; Ezh2; Pancreatic islet; α-Cells; δ-Cells

PMID:
28119131
PMCID:
PMC5494274
DOI:
10.1016/j.biocel.2017.01.008
[Indexed for MEDLINE]
Free PMC Article

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