First Author | Kane E | Year | 2024 |
Journal | iScience | Volume | 27 |
Issue | 7 | Pages | 110332 |
PubMed ID | 39055950 | Mgi Jnum | J:352077 |
Mgi Id | MGI:7704754 | Doi | 10.1016/j.isci.2024.110332 |
Citation | Kane E, et al. (2024) MicroRNA-7 regulates endocrine progenitor delamination and endocrine cell mass in developing pancreatic islets. iScience 27(7):110332 |
abstractText | beta-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 in vitro differentiation of pluripotent stem cells into beta-cells represents a viable alternative, but limitations in our current understanding of in vivo 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 in vitro differentiation and augment stem cell-derived beta-cell terminal maturity. |