title: Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts.
abstract: The extra-embryonic endoderm lineage plays a major role in the nutritive support of the embryo and is required for several inductive events, such as anterior patterning and blood island formation. Blastocyst-derived embryonic stem (ES) and trophoblast stem (TS) cell lines provide good models with which to study the development of the epiblast and trophoblast lineages, respectively. We describe the derivation and characterization of cell lines that are representative of the third lineage of the blastocyst -extra-embryonic endoderm. Extra-embryonic endoderm (XEN) cell lines can be reproducibly derived from mouse blastocysts and passaged without any evidence of senescence. XEN cells express markers typical of extra-embryonic endoderm derivatives, but not those of the epiblast or trophoblast. Chimeras generated by injection of XEN cells into blastocysts showed exclusive contribution to extra-embryonic endoderm cell types. We used female XEN cells to investigate the mechanism of X chromosome inactivation in this lineage. We observed paternally imprinted X-inactivation, consistent with observations in vivo. Based on gene expression analysis, chimera studies and imprinted X-inactivation, XEN cell lines are representative of extra-embryonic endoderm and provide a new cell culture model of an early mammalian lineage.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5, Canada.
authors.forename: Tilo
authors.initials: T
authors.lastname: Kunath
authors.forename: Danielle
authors.initials: D
authors.lastname: Arnaud
authors.forename: Gary D
authors.initials: GD
authors.lastname: Uy
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Corinne
authors.initials: C
authors.lastname: Chureau
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gardner
authors.forename: Philip
authors.initials: P
authors.lastname: Avner
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D004303:Dosage Compensation, Genetic; D004707:Endoderm / Q000502:physiology; D005260:Female; D018392:Genomic Imprinting; D006657:Histones / Q000502:physiology; D051379:Mice; D014960:X Chromosome
chemical_list: D006657:Histones