| First Author | Desgraz R | Year | 2009 |
| Journal | Development | Volume | 136 |
| Issue | 21 | Pages | 3567-74 |
| PubMed ID | 19793886 | Mgi Jnum | J:153962 |
| Mgi Id | MGI:4366655 | Doi | 10.1242/dev.039214 |
| Citation | Desgraz R, et al. (2009) Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. Development 136(21):3567-74 |
| abstractText | 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. |
