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

TL;DR

This study shows that microRNA-7 is crucial for the development of insulin-producing cells in the pancreas, which could help improve stem cell-based treatments for diabetes.

Contribution

The study identifies miR-7 as a key regulator of endocrine progenitor delamination and β-cell differentiation in the developing pancreas.

Findings

Genetic deletion of miR-7 in endocrine progenitors reduces islet endocrine cell mass.

miR-7 deficiency causes endocrine progenitors to redirect toward a ductal fate.

miR-7 is essential for efficient β-cell differentiation and terminal maturity.

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 in vitro differentiation of pluripotent stem cells into β-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 β-cell terminal maturity.

•miR-7 is expressed in delaminating progenitors in developing mouse pancreas•miR-7 KO in mouse islet endocrine progenitors leads to reduced mature cell mass•Endocrine progenitors lacking miR-7 do not delaminate, redirecting to a ductal fate•miR-7 plays a pivotal role in driving efficient β-cell differentiation

miR-7 is expressed in delaminating progenitors in developing mouse pancreas

miR-7 KO in mouse islet endocrine progenitors leads to reduced mature cell mass

Endocrine progenitors lacking miR-7 do not delaminate, redirecting to a ductal fate

miR-7 plays a pivotal role in driving efficient β-cell differentiation

Cell biology; Molecular biology; Physiology

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