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Pancreatic neurogenin 3-expressing cells are unipotent islet precursors

Published in Development. 2009, vol. 136, no. 21, p. 3567-3574
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 AnimalsBasic Helix-Loop-Helix Transcription Factors/ metabolismInsulin-Secreting Cells/cytologyIslets of Langerhans/ cytology/ growth & developmentMiceNerve Tissue Proteins/ metabolismStem Cells/cytology
PMID: 19793886
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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DESGRAZ, Renaud, HERRERA, Pedro Luis. Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. In: Development, 2009, vol. 136, n° 21, p. 3567-3574. https://archive-ouverte.unige.ch/unige:8721

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Deposited on : 2010-07-12

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