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Publication : Ductal Ngn3-expressing progenitors contribute to adult β cell neogenesis in the pancreas.

First Author  Gribben C Year  2021
Journal  Cell Stem Cell Volume  28
Issue  11 Pages  2000-2008.e4
PubMed ID  34478642 Mgi Jnum  J:343930
Mgi Id  MGI:6874761 Doi  10.1016/j.stem.2021.08.003
Citation  Gribben C, et al. (2021) Ductal Ngn3-expressing progenitors contribute to adult beta cell neogenesis in the pancreas. Cell Stem Cell 28(11):2000-2008.e4
abstractText  Ductal cells have been proposed as a source of adult beta cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal cells contribute to the beta cell population over time. Lineage tracing using the Neurogenin3 (Ngn3)-CreERT line identified ductal cells expressing the endocrine master transcription factor Ngn3 that were positive for the delta cell marker somatostatin and occasionally co-expressed insulin. The number of hormone-expressing ductal cells was increased in Akita(+/-) diabetic mice, and ngn3 heterozygosity accelerated diabetes onset. scRNA-seq of Ngn3 lineage-traced islet cells indicated that duct-derived somatostatin-expressing cells, some of which retained expression of ductal markers, gave rise to beta cells. This study identified Ngn3-expressing ductal cells as a source of adult beta cell neogenesis in homeostasis and diabetes, suggesting that this mechanism, in addition to beta cell proliferation, maintains the adult islet beta cell population.
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