title: Brief report: combined chemical treatment enables Oct4-induced reprogramming from mouse embryonic fibroblasts.
abstract: It has been established that exogenous expression of four transcription factors (Oct4, Klf4, Sox2, and c-Myc) can reprogram mammalian somatic cells to pluripotent states. Further studies demonstrated that such induced pluripotent stem cells (iPSCs) could be generated with fewer exogenous transcription factors, facilitated by endogenous expression of reprogramming factors and/or synthetic small molecules. Here, we reported identification of a new small molecule, a protein arginine methyltransferase inhibitor AMI-5, which enabled Oct4-induced reprogramming of mouse embryonic fibroblasts in combination with transforming growth factor (TGF)-β inhibitor A-83-01. The Oct4-induced iPSCs were shown similar to mouse embryonic stem cells with respect to typical pluripotency criteria. More importantly, they were shown to give rise to liveborn pups through tetraploid complementation assays, demonstrating the high quality of full reprogramming induced by this condition. Furthermore, this study suggests that regulation of protein arginine methylation might be involved in the reprogramming process.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Yuan
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wan
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Saiyong
authors.initials: S
authors.lastname: Zhu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Sheng
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects* / Q000235:genetics*; D004338:Drug Combinations; D004622:Embryo, Mammalian / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D055785:Gene Knockdown Techniques; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D000090062:Kruppel-Like Factor 4; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D051379:Mice; D008954:Models, Biological; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011484:Protein-Arginine N-Methyltransferases; D011720:Pyrazoles / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013882:Thiosemicarbazones; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
chemical_list: C507011:A-83-01; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; D011720:Pyrazoles; D013859:Thiocarbamates; D013882:Thiosemicarbazones; D016212:Transforming Growth Factor beta; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases