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

Frontiers in Cell and Developmental Biology

Xiangchen Li¹  Qiwei Ren²  Haifeng Liu³  Weijun Guan⁴  Chunyu Bai⁵  Yuhua Gao⁶ 

[1] College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&College of Basic Medicine, Jining Medical University, Jining, China;Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, China;F University, Lin’an, China;Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing China;Institute of Precision Medicine, Jining Medical University, Jining, China;

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

DOI  :  10.3389/fcell.2021.673231

来源: DOAJ

【 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.ConclusionThis study describes a novel approach for beta cell production and supports the use of iPSCs for cell replacement therapy of T1DM.

【 授权许可】

Unknown