title: Establishment of a primed pluripotent epiblast stem cell in FGF4-based conditions.
abstract: Several mouse pluripotent stem cell types have been established either from mouse blastocysts and epiblasts. Among these, embryonic stem cells (ESCs) are considered to represent a "naïve", epiblast stem cells (EpiSCs) a "primed" pluripotent state. Although EpiSCs form derivatives of all three germ layers during in vitro differentiation, they rarely incorporate into the inner cell mass of blastocysts and rarely contribute to chimera formation following blastocyst injection. Here we successfully established homogeneous population of EpiSC lines with efficient chimera-forming capability using a medium containing fibroblast growth factor (FGF)-4. The expression levels of Rex1 and Nanog was very low although Oct4 level is comparable to ESCs. EpiSCs also expressed higher levels of epiblast markers, such as Cer1, Eomes, Fgf5, Sox17, and T, and further showed complete DNA methylation of Stella and Dppa5 promoters. However, the EpiSCs were clustered separately from E3 and T9 EpiSC lines and showed a completely different global gene expression pattern to ESCs. Furthermore, the EpiSCs were able to differentiate into all three germ layers in vitro and efficiently formed teratomas and chimeric embryos (21.4%) without germ-line contribution.
authors.affiliation: 1] Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany [2] Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea [3] Infertility Clinic Center, Haesung Hospital, Chun An 331-950, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Joo
authors.affiliation: Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Choi
authors.affiliation: Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Holm
authors.initials: H
authors.lastname: Zaehres
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stehling
authors.affiliation: Infertility Clinic Center, Haesung Hospital, Chun An 331-950, Republic of Korea.
authors.forename: Koo Sung
authors.initials: KS
authors.lastname: Jung
authors.affiliation: Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D051519:Fibroblast Growth Factor 4 / Q000235:genetics*; D005855:Germ Layers / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C513672:Zfp42 protein, mouse; D014157:Transcription Factors