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Scientific article
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Pancreatic neurogenin 3-expressing cells are unipotent islet precursors

Published inDevelopment, vol. 136, no. 21, p. 3567-3574
Publication date2009
Abstract

Pancreatic islet endocrine cells arise during development from precursors expressing neurogenin 3 (Ngn3). As a population, Ngn3(+) cells produce all islet cell types, but the potential of individual Ngn3(+) cells, an issue central to organogenesis in general and to in vitro differentiation towards cell-based therapies, has not been addressed. We performed in vivo clonal analyses in mice to study the proliferation and differentiation of very large numbers of single Ngn3(+) cells using MADM, a genetic system in which a Cre-dependent chromosomal translocation labels, at extremely low mosaic efficiency, a small number of Ngn3(+) cells. We scored large numbers of progeny arising from single Ngn3(+) cells. In newborns, labeled islets frequently contained just a single tagged endocrine cell, indicating for the first time that each Ngn3(+) cell is the precursor of a single endocrine cell. In adults, small clusters of two to three Ngn3(+) progeny were detected, but all expressed the same hormone, indicating a low rate of replication from birth to adult stages. We propose a model whereby Ngn3(+) cells are monotypic (i.e. unipotent) precursors, and use this paradigm to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans.

Keywords
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/ metabolism
  • Insulin-Secreting Cells/cytology
  • Islets of Langerhans/ cytology/ growth & development
  • Mice
  • Nerve Tissue Proteins/ metabolism
  • Stem Cells/cytology
Citation (ISO format)
DESGRAZ, Renaud, HERRERA, Pedro Luis. Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. In: Development, 2009, vol. 136, n° 21, p. 3567–3574. doi: 10.1242/dev.039214
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ISSN of the journal0950-1991
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