Exocrine-to-endocrine differentiation is detectable only prior to birth in the uninjured mouse pancreas
Open Access
- 8 April 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Developmental Biology
- Vol. 10 (1), 38
- https://doi.org/10.1186/1471-213x-10-38
Abstract
Background: Histological evidence suggests that insulin-producing beta (β)-cells arise in utero from duct-like structures of the fetal exocrine pancreas, and genetic lineage tracing studies indicate that they are maintained in the adult by self-renewal. These studies have not addressed the origin of the new β-cells that arise in large numbers shortly after birth, and contradictory lineage tracing results have been published regarding the differentiation potential of duct cells in this period. We established an independent approach to address this question directly. Results: We generated mice in which duct and acinar cells, comprising the exocrine pancreas, can be genetically marked by virtue of their expressing the mucin gene Muc1. Using these mice, we performed time-specific lineage tracing to determine if these cells undergo endocrine transdifferentiation in vivo. We find that Muc1+ cells do give rise to β-cells and other islet cells in utero, providing formal proof that mature islets arise from embryonic duct structures. From birth onwards, Muc1 lineage-labeled cells are confined to the exocrine compartment, with no detectable contribution to islet cells. Conclusions: These results argue against a significant contribution by exocrine transdifferentiation to the normal postnatal expansion and maintenance of β-cell mass. Exocrine transdifferentiation has been proposed to occur during injury and regeneration, and our experimental model is suited to test this hypothesis in vivo.Keywords
This publication has 45 references indexed in Scilit:
- Ductal Origin Hypothesis of Pancreatic Regeneration under AttackCell Metabolism, 2010
- Pancreatic Exocrine Duct Cells Give Rise to Insulin-Producing β Cells during Embryogenesis but Not after BirthDevelopmental Cell, 2009
- Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birthProceedings of the National Academy of Sciences of the United States of America, 2008
- β-Cell Proliferation, but Not Neogenesis, Following 60% Partial Pancreatectomy Is Impaired in the Absence of FoxM1Diabetes, 2008
- Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on SurvivinDiabetes, 2008
- Recovery from diabetes in mice by β cell regenerationJCI Insight, 2007
- All β Cells Contribute Equally to Islet Growth and MaintenancePLoS Biology, 2007
- Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regenerationJCI Insight, 2007
- Regulation of Cre Recombinase Activity by Mutated Estrogen Receptor Ligand-Binding DomainsBiochemical and Biophysical Research Communications, 1997
- Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.Proceedings of the National Academy of Sciences of the United States of America, 1993