title: Isolation of epiblast stem cells from preimplantation mouse embryos.
abstract: Pluripotent stem cells provide a platform to interrogate control elements that function to generate all cell types of the body. Despite their utility for modeling development and disease, the relationship of mouse and human pluripotent stem cell states to one another remains largely undefined. We have shown that mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) are distinct, pluripotent states isolated from pre- and post-implantation embryos respectively. Human ES cells are different than mouse ES cells and share defining features with EpiSCs, yet are derived from pre-implantation human embryos. Here we show that EpiSCs can be routinely derived from pre-implantation mouse embryos. The preimplantation-derived EpiSCs exhibit molecular features and functional properties consistent with bona fide EpiSCs. These results provide a simple method for isolating EpiSCs and offer direct insight into the intrinsic and extrinsic mechanisms that regulate the acquisition of distinct pluripotent states.
authors.affiliation: Department of Genetics & Center for Stem Cell and Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Najm
authors.forename: Josh G
authors.initials: JG
authors.lastname: Chenoweth
authors.forename: Philip D
authors.initials: PD
authors.lastname: Anderson
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Nadeau
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Redline
authors.forename: Ronald D G
authors.initials: RD
authors.lastname: McKay
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Tesar
mesh_terms: D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002469:Cell Separation / Q000379:methods*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism