title: Reprogramming of mouse and human somatic cells by high-performance engineered factors.
abstract: Reprogramming somatic cells to become induced pluripotent stem cells (iPSCs) by using defined factors represents an important breakthrough in biology and medicine, yet remains inefficient and poorly understood. We therefore devised synthetic factors by fusing the VP16 transactivation domain to OCT4 (also known as Pou5f1), NANOG and SOX2, respectively. These synthetic factors could reprogramme both mouse and human fibroblasts with enhanced efficiency and accelerated kinetics. Remarkably, Oct4-VP16 alone could efficiently reprogramme mouse embryonic fibroblasts (MEFs) into germline-competent iPSCs. Furthermore, episomally delivered synthetic factors could reproducibly generate integration-free iPSCs from MEFs with enhanced efficiency. Our results not only demonstrate the feasibility of engineering more potent reprogramming factors, but also suggest that transcriptional reactivation of OCT4 target genes might be a rate-limiting step in the conversion of somatic cells to pluripotent cells. Synthetic factor-based reprogramming might lead to a paradigm shift in reprogramming research.
authors.affiliation: The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiekai
authors.initials: J
authors.lastname: Chen
authors.forename: Jia-Lei
authors.initials: JL
authors.lastname: Hu
authors.forename: Xi-Xiao
authors.initials: XX
authors.lastname: Wei
authors.forename: Dajiang
authors.initials: D
authors.lastname: Qin
authors.forename: Juan
authors.initials: J
authors.lastname: Gao
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Ke-Yu
authors.initials: KY
authors.lastname: Lai
authors.forename: Xia
authors.initials: X
authors.lastname: Kuang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Duanqing
authors.initials: D
authors.lastname: Pei
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Xu
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors