title: MiR-134-Mbd3 axis regulates the induction of pluripotency.
abstract: MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression and play an important role in reprogramming process; however, relatively little is known about the underlying regulatory mechanism of miRNAs on how they epigenetically modulate reprogramming and pluripotency. Here, we report that the expression level of microRNA-134 (miR-134) was low in mouse embryonic stem cells (mESCs) but significantly up-regulated during neural differentiation, while down-regulated during the induction of induced pluripotent stem cells (iPSCs) from neural progenitor cells (NPCs). Inhibition of miR-134 by miR-134 sponge promoted the efficiency of reprogramming which also was highly similar to mESCs. On the contrary, up-regulation of miR-134 repressed iPSCs induction. We also found that inhibition of miR-134 promoted the maturation of pre-iPSCs and increased its pluripotency. We also showed that miR-134 can directly target to the pluripotency related factor Methyl-CpG-binding domain protein 3 (Mdb3) 3' untranslated regions (3' UTR) to down-regulate its expression. And Mbd3 was found to promote the induction of iPSCs and could block the repression of reprogramming caused by overexpression of miR-134. This work revealed the critical function of miR-134-Mbd3 axis on regulating reprogramming and pluripotency of iPSCs derived from the NPCs, and might provide an insight into the miR-134-Mbd3 axis on regulating the iPSCs quality for further clinical treatment.
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C492013:Mbd3 protein, mouse; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D014157:Transcription Factors
keywords: Mbd3; induced pluripotent stem cells (iPSCs); miR-134; neural progenitor cells (NPCs)