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Neurogenin 3(+) cells contribute to beta-cell neogenesis and proliferation in injured adult mouse pancreas
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2013 (English)In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 4, e523- p.Article in journal (Refereed) Published
Abstract [en]

We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to beta cells ex vivo. Here we evaluate the role of Ngn3(+) cells in beta cell expansion in situ. PDL not only induced doubling of the beta cell volume but also increased the total number of islets. beta cells proliferated without extended delay (the so-called 'refractory' period), their proliferation potential was highest in small islets, and 86% of the beta cell expansion was attributable to proliferation of pre-existing beta cells. At sufficiently high Ngn3 expression level, upto 14% of all beta cells and 40% of small islet beta cells derived from non-beta cells. Moreover, beta cell proliferation was blunted by a selective ablation of Ngn3(+) cells but not by conditional knockout of Ngn3 in pre-existing beta cells supporting a key role for Ngn3(+) insulin(-) cells in beta cell proliferation and expansion. We conclude that Ngn3(+) cell-dependent proliferation of pre-existing and newly-formed beta cells as well as reprogramming of non-beta cells contribute to in vivo beta cell expansion in the injured pancreas of adult mice.

Place, publisher, year, edition, pages
London: Nature Publishing Group, 2013. Vol. 4, e523- p.
Keyword [en]
diabetes, cell differentiation, tissue injury
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-70152DOI: 10.1038/cddis.2013.52ISI: 000316868700002OAI: oai:DiVA.org:umu-70152DiVA: diva2:620549
Available from: 2013-05-08 Created: 2013-05-06 Last updated: 2017-12-06Bibliographically approved

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Eriksson, MariaSvensson, ChristofferAhlgren, Ulf
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