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

• DOI: 10.1016/j.stem.2021.08.003
• Publication Date: 2021-09-02T14:44:42Z
• Authors: Christopher Gribben; Christopher Lambert; Hendrik A. Messal; Ella-Louise Hubber; Chloe Rackham; Ian Evans; Harry Heimberg; Peter Jones; Rocio Sancho; Axel Behrens
• Keywords: Ductal cells; Neogenesis; Enteroendocrine cell

Ductal cells have been proposed as a source of adult β 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 contribute to the population over time. Lineage tracing using Neurogenin3 (Ngn3)-CreERT line identified expressing endocrine master transcription factor Ngn3 were positive for δ marker somatostatin occasionally co-expressed insulin. The number hormone-expressing was increased in Akita+/− diabetic mice, ngn3 heterozygosity accelerated diabetes onset. scRNA-seq lineage-traced islet indicated duct-derived somatostatin-expressing cells, some which retained expression markers, gave rise cells. This study Ngn3-expressing neogenesis homeostasis diabetes, suggesting mechanism, addition proliferation, maintains population.