title: Two Histone Variants TH2A and TH2B Enhance Human Induced Pluripotent Stem Cell Generation.
abstract: There are two major methods of reprogramming: generation of induced pluripotent stem cells (iPSCs) by overexpressing embryonic stem cell-specific transcription factors (OCT4, SOX2, KLF4, and c-MYC) and somatic cell nuclear transfer by oocyte-specific factors. Previously, we reported oocyte-enriched histone variants TH2A, TH2B, and the histone chaperone nucleoplasmin (NPM2) enhance the reprogramming by OSKM in mice by inducing open chromatin structure. In this study, we showed that human TH2A, TH2B, and NPM2 enhance the OSKM-induced reprogramming of adult and neonatal human dermal fibroblasts and umbilical vein endothelial cells. Pluripotency of iPSCs generated by coexpressing OSKM, TH2A, TH2B, and NPM2 was shown by in vitro and in vivo differentiation assays. These iPSCs gave rise to highly differentiated teratomas compared to iPSCs induced by OSKM alone. Genome-wide analysis suggests a possibility that TH2A, TH2B, and NPM2 might regulate genes that are involved in naïve stem cell stage. Thus, TH2A, TH2B, and NPM2 enhance reprogramming of human somatic cells and improve the quality of human iPSCs.
authors.affiliation: 1 Laboratory of Molecular Genetics, RIKEN Tsukuba Institute , Tsukuba, Japan .|2 CREST Research Project of JST (Japan Science and Technology Agency) , Tsukuba, Japan .|3 Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Japan .
authors.forename: Linh My
authors.initials: LM
authors.lastname: Huynh
authors.affiliation: 1 Laboratory of Molecular Genetics, RIKEN Tsukuba Institute , Tsukuba, Japan .|2 CREST Research Project of JST (Japan Science and Technology Agency) , Tsukuba, Japan .|3 Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Japan .
authors.forename: Toshie
authors.initials: T
authors.lastname: Shinagawa
authors.affiliation: 1 Laboratory of Molecular Genetics, RIKEN Tsukuba Institute , Tsukuba, Japan .|2 CREST Research Project of JST (Japan Science and Technology Agency) , Tsukuba, Japan .|3 Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Japan .
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
mesh_terms: D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D056489:Nucleoplasmins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C533550:NPM2 protein, human; D056489:Nucleoplasmins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors