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

Ductal cells have been proposed as a source of adult ß 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 ß 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 δ 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 ß cells. This study identified Ngn3-expressing ductal cells as a source of adult ß cell neogenesis in homeostasis and diabetes, suggesting that this mechanism, in addition to ß cell proliferation, maintains the adult islet ß cell population.

Bench to bedside: Current advances in regenerative medicine.

Regenerative medicine is a diverse and rapidly evolving field, employing core expertise from biologists, engineers, and clinicians. Recently the field has made significant progress towards regenerating or replacing tissues lost to age, disease or injury. Current strategies include transplantation of adult or pluripotent stem cells to replace tissue or support tissue healing. Promising approaches for the future of regenerative medicine include stimulating endogenous stem cells for in situ repair, transplantation of organoids to repair minor tissue injury, and the use of interspecies chimerism to produce functional metabolic organs for transplantation. In our review we focus on these emerging strategies, paying particular attention to their current and prospective translational impacts and challenges.