MicroRNA-7 regulates endocrine progenitor delamination and endocrine cell mass in developing pancreatic islets

Abstract

β-cell replenishment in patients with diabetes through cadaveric islet transplantation has been successful; however, it requires long-term immunosuppression and suitable islet donors are scarce. Stepwise invitro differentiation of pluripotent stem cells into β-cells represents a viable alternative, but limitations in our current understanding of invivo islet endocrine differentiation constrains its clinical use. Here, we show that microRNA-7 (miR-7) is highly expressed in embryonic pancreatic endocrine progenitors. Genetic deletion of the miR-7 gene family in endocrine progenitors leads to reduced islet endocrine cell mass, due to endocrine progenitors failing to delaminate from the epithelial plexus. This is associated with a reduction in neurogenin-3 levels and increased expression of Sry-box transcription factor 9. Further, we observe that a significant number of endocrine progenitors lacking miR-7 differentiate into ductal cells. Our study suggests that increasing miR-7 expression could improve efficiency of invitro differentiation and augment stem cell-derived β-cell terminal maturity.