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J Cell Biol. 2017 Dec 4;216(12):4299-4311. doi: 10.1083/jcb.201704044. Epub 2017 Oct 12.

Ectopic expression of Pax4 in pancreatic δ cells results in β-like cell neogenesis.

Author information

1
Université Côte d'Azur, Institut National de la Santé et de la Recherche Medicale, Centre National de la Recherche Scientifique, Institut Biologie Valrose, Nice, France.
2
EVOTEC International, Göttingen, Germany.
3
Novartis Pharmaceuticals, Basel, Switzerland.
4
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
5
Department of Clinical Neurophysiology, University of Göttingen, Göttingen, Germany.
6
Université Côte d'Azur, Institut National de la Santé et de la Recherche Medicale, Centre National de la Recherche Scientifique, Institut Biologie Valrose, Nice, France collombat@unice.fr.

Abstract

The recent demonstration that pancreatic α cells can be continuously regenerated and converted into β-like cells upon ectopic expression of Pax4 opened new avenues of research in the endocrine cell differentiation and diabetes fields. To determine whether such plasticity was also shared by δ cells, we generated and characterized transgenic animals that express Pax4 specifically in somatostatin-expressing cells. We demonstrate that the ectopic expression of Pax4 in δ cells is sufficient to induce their conversion into functional β-like cells. Importantly, this conversion induces compensatory mechanisms involving the reactivation of endocrine developmental processes that result in dramatic β-like cell hyperplasia. Importantly, these β-like cells are functional and can partly reverse the consequences of chemically induced diabetes.

PMID:
29025873
PMCID:
PMC5716283
DOI:
10.1083/jcb.201704044
[Indexed for MEDLINE]
Free PMC Article

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