title: Reduced oxygen concentration enhances conversion of embryonic stem cells to epiblast stem cells.
abstract: Recently, an additional type of pluripotent stem cell-line derived from mouse embryos has been established and termed epiblast stem cell (EpiSC), and is expected to be an important tool for studying the mechanisms of maintenance of pluripotency since they depend on basic fibroblast growth factor-MAPK and Activin A-Smad2/3 signaling to maintain pluripotency, unlike mouse embryonic stem cells (ESCs). Further, because of the similarities between mouse EpiSCs and human ESCs, EpiSCs are expected to be effective experimental models for human stem cell therapy. Recently, study for conversion from ESC state to EpiSC state or reversion from EpiSC state to ESC state has attracted interest since these techniques may lead to increasing the potential of pluripotent stem cells and our knowledge about their developmental status. In the present study, we find that a low oxygen concentration in culture environment accelerated, improved, and stabilized the EpiSC state of the converted cells from the ESC state using Oct4ΔPE-GFP transgenic ESCs. Induced EpiSCs (iEpiSCs) in hypoxia possess closer gene expression patterns to native EpiSCs, and bisulfite sequences for the promoter regions of Stella and Oct4 genes have elucidated that the iEpiSC gain EpiSC-specific methylation patterns in hypoxia. Our data provide evidence that oxygen concentration is an important factor for establishment of the EpiSC-specific state.
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kinki University Faculty of Medicine, Osaka, Japan. teramura@med.kindai.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takehara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Teramura
authors.forename: Yuta
authors.initials: Y
authors.lastname: Onodera
authors.forename: Chiaki
authors.initials: C
authors.lastname: Hamanishi
authors.forename: Kanji
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D005855:Germ Layers / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003470:Culture Media; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D049452:Green Fluorescent Proteins; D053612:Janus Kinases; D010100:Oxygen