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. |