title: Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1.
abstract: Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4. However, the conversion to iPSCs is inefficient. The proto-oncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs. Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the generation of iPSCs from both mouse and human fibroblasts when it is expressed together with OSK. Mouse iPSCs generated using this combination of transcription factors can form germline-competent chimaeras. Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal-epithelial transition. These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Maekawa
authors.forename: Kei
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ran
authors.initials: R
authors.lastname: Shibukawa
authors.forename: Ikumi
authors.initials: I
authors.lastname: Kodanaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichisaka
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.forename: Shinya
authors.initials: S
authors.lastname: Yamanaka
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D016259:Genes, myc / Q000235:genetics; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051379:Mice; D000071317:Nanog Homeobox Protein; D053652:Nuclear Transfer Techniques; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C098925:Esrrb protein, mouse; C496503:Foxa2 protein, mouse; C508055:GLIS1 protein, human; C559647:Glis1 protein, mouse; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C488352:Lin-28 protein, mouse; C000715470:MAS1 protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D000090063:Proto-Oncogene Mas; D016601:RNA-Binding Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta