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Pancreatic neurogenin 3-expressing cells are unipotent islet precursors
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| Zeitschriftentitel: | Development |
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| Personen und Körperschaften: | , |
| In: | Development, 136, 2009, 21, S. 3567-3574 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Company of Biologists
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>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.</jats:p> |
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| Umfang: | 3567-3574 |
| ISSN: |
1477-9129
0950-1991 |
| DOI: | 10.1242/dev.039214 |