title: Involvement of Polycomb Repressive Complex 2 in Maturation of Induced Pluripotent Stem Cells during Reprogramming of Mouse and Human Fibroblasts.
abstract: Induced pluripotent stem cells (iPSCs) provide a reliable source for the study of regenerative medicine, drug discovery, and developmental biology. Despite extensive studies on the reprogramming of mouse and human fibroblasts into iPSCs, the efficiency of reprogramming is still low. Here, we used a bioinformatics and systems biology approach to study the two gene regulatory waves governing the reprogramming of mouse and human fibroblasts into iPSCs. Our results revealed that the maturation phase of reprogramming was regulated by a more complex regulatory network of transcription factors compared to the initiation phase. Interestingly, in addition to pluripotency factors, the polycomb repressive complex 2 (PRC2) members Ezh2, Eed, Jarid2, Mtf2, and Suz12 are crucially recruited during the maturation phase of reprogramming. Moreover, we found that during the maturation phase of reprogramming, pluripotency factors, via the expression and induction of PRC2 complex members, could silence the lineage-specific gene expression program and maintain a ground state of pluripotency in human and mouse naïve iPSCs. The findings obtained here provide us a better understanding of the gene regulatory network (GRN) that governs reprogramming, and the maintenance of the naïve state of iPSCs.
authors.affiliation: Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Niusha
authors.initials: N
authors.lastname: Khazaie
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON, Canada.|Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Massumi
authors.affiliation: Department of Medical Genetics and Signal Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Wee
authors.affiliation: Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mahdieh
authors.initials: M
authors.lastname: Salimi
authors.affiliation: Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Abdulshakour
authors.initials: A
authors.lastname: Mohammadnia
authors.affiliation: Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Moein
authors.initials: M
authors.lastname: Yaqubi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D060066:Protein Interaction Maps / Q000235:genetics
chemical_list: D063151:Polycomb Repressive Complex 2