The miR-590/Acvr2a/Terf1 Axis Regulates Telomere Elongation and Pluripotency of Mouse iPSCs

• Published in: Stem cell reports Vol. 11; no. 1; pp. 88 - 101
• Main Authors: Liu, Qidong, Wang, Guiying, Lyu, Yao, Bai, Mingliang, Jiapaer, Zeyidan, Jia, Wenwen, Han, Tong, Weng, Rong, Yang, Yiwei, Yu, Yangyang, Kang, Jiuhong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.07.2018; Elsevier
• Subjects: Activin Receptors, Type II - genetics; Activin Receptors, Type II - metabolism; Acvr2a; Animals; Cell Differentiation - genetics; Cell Line; Cell Self Renewal - genetics; Gene Expression Regulation, Developmental; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; iPSCs; Mice; MicroRNAs - genetics; miR-590; pluripotency; RNA Interference; telomere; Telomere - genetics; Telomere - metabolism; Telomere Homeostasis - genetics; Telomeric Repeat Binding Protein 1 - genetics; Telomeric Repeat Binding Protein 1 - metabolism; Terf1; Acvr2a; iPSCs; miR-590; Terf1; pluripotency; telomere
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2018.05.008

During reprogramming, telomere re-elongation is important for pluripotency acquisition and ensures the high quality of induced pluripotent stem cells (iPSCs), but the regulatory mechanism remains largely unknown. Our study showed that fully reprogrammed mature iPSCs or mouse embryonic stem cells expressed higher levels of miR-590-3p and miR-590-5p than pre-iPSCs. Ectopic expression of either miR-590-3p or miR-590-5p in pre-iPSCs improved telomere elongation and pluripotency. Activin receptor II A (Acvr2a) is the downstream target and mediates the function of miR-590. Downregulation of Acvr2a promoted telomere elongation and pluripotency. Overexpression of miR-590 or inhibition of ACTIVIN signaling increased telomeric repeat binding factor 1 (Terf1) expression. The p-SMAD2 showed increased binding to the Terf1 promoter in pre-iPSCs compared with mature iPSCs. Downregulation of Terf1 blocked miR-590- or shAcvr2a-mediated promotion of telomere elongation and pluripotency in pre-iPSCs. This study elucidated the role of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. [Display omitted] •miR-590 is critical for telomere elongation and pluripotency of pre-iPSCs•miR-590 can target Acvr2a to upregulate the expression of Terf1•miR-590/Acvr2a/Terf1 axis regulates the elongation and pluripotency of pre-iPSCs In this article, Kang and colleagues elucidate the critical function and regulatory mechanism of the miR-590/Acvr2a/Terf1 signaling pathway in modulating telomere elongation and pluripotency in pre-iPSCs. These findings not only determined the miR-590/Acvr2a/Terf1 axis on regulating both telomere elongation and pluripotency but also revealed an underlying mechanism pushing forward the maturation of the pre-iPSCs.