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Dev Cell. 2013 Jul 15;26(1):86-100. doi: 10.1016/j.devcel.2013.05.018. Epub 2013 Jun 27.

Adult duct-lining cells can reprogram into β-like cells able to counter repeated cycles of toxin-induced diabetes.

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1
Université de Nice-Sophia Antipolis, FR-06108 Nice, France.

Abstract

It was recently demonstrated that embryonic glucagon-producing cells in the pancreas can regenerate and convert into insulin-producing β-like cells through the constitutive/ectopic expression of the Pax4 gene. However, whether α cells in adult mice display the same plasticity is unknown. Similarly, the mechanisms underlying such reprogramming remain unclear. We now demonstrate that the misexpression of Pax4 in glucagon(+) cells age-independently induces their conversion into β-like cells and their glucagon shortage-mediated replacement, resulting in islet hypertrophy and in an unexpected islet neogenesis. Combining several lineage-tracing approaches, we show that, upon Pax4-mediated α-to-β-like cell conversion, pancreatic duct-lining precursor cells are continuously mobilized, re-express the developmental gene Ngn3, and successively adopt a glucagon(+) and a β-like cell identity through a mechanism involving the reawakening of the epithelial-to-mesenchymal transition. Importantly, these processes can repeatedly regenerate the whole β cell mass and thereby reverse several rounds of toxin-induced diabetes, providing perspectives to design therapeutic regenerative strategies.

PMID:
23810513
DOI:
10.1016/j.devcel.2013.05.018
[Indexed for MEDLINE]
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