Neurogenin 3+ cells contribute to β-cell neogenesis and proliferation in injured adult mouse pancreas.

Abstract:

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

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Van de Casteele M,Leuckx G,Baeyens L,Cai Y,Yuchi Y,Coppens V,De Groef S,Eriksson M,Svensson C,Ahlgren U,Ahnfelt-Rønne J,Madsen OD,Waisman A,Dor Y,Jensen JN,Heimberg H

doi

10.1038/cddis.2013.52

subject

Has Abstract

pub_date

2013-03-07 00:00:00

pages

e523

issn

2041-4889

pii

cddis201352

journal_volume

4

pub_type

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