title: microRNA-29b is a novel mediator of Sox2 function in the regulation of somatic cell reprogramming.
abstract: Fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSCs) by the application of Yamanaka factors (OSKM), but the mechanisms underlying this reprogramming remain poorly understood. Here, we report that Sox2 directly regulates endogenous microRNA-29b (miR-29b) expression during iPSC generation and that miR-29b expression is required for OSKM- and OSK-mediated reprogramming. Mechanistic studies show that Dnmt3a and Dnmt3b are in vivo targets of miR-29b and that Dnmt3a and Dnmt3b expression is inversely correlated with miR-29b expression during reprogramming. Moreover, the effect of miR-29b on reprogramming can be blocked by Dnmt3a or Dnmt3b overexpression. Further experiments indicate that miR-29b-DNMT signaling is significantly involved in the regulation of DNA methylation-related reprogramming events, such as mesenchymal-to-epithelial transition (MET) and Dlk1-Dio3 region transcription. Thus, our studies not only reveal that miR-29b is a novel mediator of reprogramming factor Sox2 but also provide evidence for a multistep mechanism in which Sox2 drives a miR-29b-DNMT signaling axis that regulates DNA methylation-related events during reprogramming.
authors.affiliation: Clinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Guo
authors.forename: Qidong
authors.initials: Q
authors.lastname: Liu
authors.forename: Guiying
authors.initials: G
authors.lastname: Wang
authors.forename: Songcheng
authors.initials: S
authors.lastname: Zhu
authors.forename: Longfei
authors.initials: L
authors.lastname: Gao
authors.forename: Wujun
authors.initials: W
authors.lastname: Hong
authors.forename: Yafang
authors.initials: Y
authors.lastname: Chen
authors.forename: Minjuan
authors.initials: M
authors.lastname: Wu
authors.forename: Houqi
authors.initials: H
authors.lastname: Liu
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D058750:Epithelial-Mesenchymal Transition; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013724:Teratoma / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D035683:MicroRNAs; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D000097584:DNA Methyltransferase 3B; C000715535:Dnmt3a protein, mouse; C547014:MIRN29 microRNA, mouse