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
第一作者: Bai, Chunyu
作者: Bai, Chunyu;Gao, Yuhua;Bai, Chunyu;Guan, Weijun;Gao, Yuhua;Ren, Qiwei;Liu, Haifeng;Li, Xiangchen
作者机构:
关键词: iPSCs; beta cells; differentiation; extracellular vesicles; miRNAs
期刊名称:FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY ( 影响因子:6.684; 五年影响因子:7.219 )
ISSN: 2296-634X
年卷期: 2021 年 9 卷
页码:
收录情况: SCI
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.
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