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

M. Van De Casteele, G. Leuckx, L. Baeyens, Y. Cai, Y. Yuchi, V. Coppens, S. De Groef, M. Eriksson, C. Svensson, U. Ahlgren, J. Ahnfelt-Ronne, O. D. Madsen, A. Waisman, Y. Dor, J. N. Jensen, H. Heimberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

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 Ngn 3++ 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-b cells. Moreover, β cell proliferation was blunted by a selective ablation of Ngn3++ cells but not by conditional knockout of Ngn 3+ in pre-existing β cells supporting a key role for Ngn 3++ 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-b cells contribute to in vivo β cell expansion in the injured pancreas of adult mice.

Original languageAmerican English
Pages (from-to)e523
JournalCell Death and Disease
Volume4
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • Cell differentiation
  • Diabetes
  • Tissue injury

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