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miR-212/132-Enriched Extracellular Vesicles Promote Differentiation of Induced Pluripotent Stem Cells Into Pancreatic Beta Cells

文献类型： 外文期刊

作者： Chunyu Bai;Qiwei Ren;Haifeng Liu;Xiangchen Li;Weijun Guan;Yuhua Gao

作者机构：

关键词： beta cells;differentiation;extracellular vesicles;iPSCs;miRNAs

期刊名称： Frontiers in Cell and Developmental Biology

ISSN： 2296-634X

年卷期： 2021 年 9.0 卷

页码：

收录情况： JCR（2021版）

摘要： Pancreatic beta cell transplantation is the ideal method for treatment of type 1 diabetes mellitus (T1DM), and the generation of beta cells from induced pluripotent stem cells (iPSCs) of patients is a promising strategy. In this study, we improved a previous strategy to produce beta cells using extracellular vesicles (EVs) derived from mature beta cells and differentiated beta cells from iPSCs (i-Beta cells), which secreted insulin under glucose stimulation in vitro and ameliorated hyperglycemia in vivo. Mechanistic analyses revealed that EV-carried microRNA (miR)-212/132 (EV-miR-212/132) directly bound to the 3′ UTR of FBW7 to prevent its translation and FBW7 combined with NGN3 to accelerate its proteasomal degradation. EV-miR-212/132 stabilized NGN3 expression to promote differentiation of endocrine cells from induced iPSCs. Moreover, NGN3 bound to PDX1 to enhance transcription of endogenous miR-212/132 and formed a positive regulatory circuit that maintained the functions of mature pancreatic beta cells. Conclusion: This study describes a novel approach for beta cell production and supports the use of iPSCs for cell replacement therapy of T1DM. © Copyright © 2021 Bai, Ren, Liu, Li, Guan and Gao.

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