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

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.
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