title: Epigenetic Modifiers Facilitate Induction and Pluripotency of Porcine iPSCs.
abstract: Inadequate silencing of exogenous genes represents a major obstacle to complete epigenetic reprogramming of porcine-induced pluripotent stem cells (piPSCs) by conventional pluripotency transcription factors (OSKM). We tested the hypothesis that epigenetic modification by active DNA or histone demethylation or by inhibition of histone deacetylase would enhance reprogramming and exogenous gene silencing in piPSCs. piPSCs induced by OSKM in combination with epigenetic factors, specifically Ten-Eleven Translocation (Tet1 or Tet3) or lysine (K)-specific demethylase 3A (Kdm3a), expressed higher levels of Rex1 and other genes representing naive state and exhibited more open chromatin status, compared with those of OSKM controls. Tet1 also improved differentiation capacity. Conversion with inhibitors of histone deacetylases (HDACi), NaB, TSA, or VPA, further increased Rex1 expression, while decreasing expression of exogenous genes. piPSCs induced by Tet1+OSKM followed by conversion with HDACi show high pluripotency. Together, epigenetic modifiers enhance generation of piPSCs and reduce their reliance on exogenous genes.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xumin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: liulin@nankai.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D000066673:Cell Self Renewal / Q000187:drug effects / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D065150:Cellular Reprogramming; D044127:Epigenesis, Genetic / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D013552:Swine; D013724:Teratoma / Q000235:genetics / Q000473:pathology
chemical_list: D056572:Histone Deacetylase Inhibitors; D051741:Kruppel-Like Transcription Factors
keywords: epigenetics; iPSC; porcine; reprogramming