title: Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family.
abstract: Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4, and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in induced pluripotent stem cells (iPSCs) have been shown to be highly similar to embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern when using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming. Here, we found that the miR-29 family is an important epigenetic regulator during human somatic cell reprogramming. Our global DNA methylation and hydroxymethylation analysis shows that DNA demethylation is a major event mediated by miR-29a depletion during early reprogramming, and that iPSCs derived from miR-29a depletion are epigenetically closer to ESCs. Our findings uncover an important miRNA-based approach to generate clinically robust iPSCs.
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Eriona
authors.initials: E
authors.lastname: Hysolli
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Cell Biology, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Kun-Yong
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, 975 Northeast, 10th Street, Oklahoma City, OK 73104, USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Janknecht
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, 515041, P.R. China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Geng
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Caihong
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA; Department of Obstetrics and Gynecology, CHA Gangnam Medical Center, CHA University, Seoul 135-081, Republic of Korea.
authors.forename: Yong-Wook
authors.initials: YW
authors.lastname: Jung
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Jijun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Cell Biology, Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA.
authors.forename: Sherman M
authors.initials: SM
authors.lastname: Weissman
authors.affiliation: Department of Genetics, Yale Stem Cell Center, Yale School of Medicine, 10 Amistad, 201B, New Haven, CT 06520, USA. Electronic address: inhyun.park@yale.edu.
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Park
mesh_terms: D065150:Cellular Reprogramming / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C532045:MIRN29a microRNA, human; D035683:MicroRNAs