title: Choice of random rather than imprinted X inactivation in female embryonic stem cell-derived extra-embryonic cells.
abstract: In female mammals, one of two X chromosomes is epigenetically inactivated for gene dosage compensation, known as X inactivation (Xi). Inactivation occurs randomly in either the paternal or maternal X chromosome in all embryonic cell lineages, designated as random Xi. By contrast, in extra-embryonic cell lineages, which are segregated from somatic cell lineages in pre-implantation development, the paternal X chromosome is selectively inactivated, known as imprinted Xi. Although it is speculated that erasure of the imprinted mark on either the maternal or paternal X chromosome in somatic cell lineages might change the mode of Xi from imprinted to random, it is not known when this event is completed in development. Here, we tested the mode of Xi during the differentiation of female mouse embryonic stem (ES) cells derived from the inner cell mass (ICM) of blastocyst-stage embryos toward trophectoderm (TE) and primitive endoderm (PrE) lineages induced by artificial activation of transcription factor genes Cdx2 and Gata6, respectively. We found that random Xi occurs in both TE and PrE cells. Moreover, cloned embryos generated by the transfer of nuclei from the female ES cells showed random Xi in TE, suggesting the complete erasure of all X imprints for imprinted Xi in ICM-derived ES cells.
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology (CDB), Kobe, Hyogo 650-0047, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtsuka
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
mesh_terms: D000818:Animals; D053624:Blastocyst Inner Cell Mass / Q000166:cytology; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics; D004475:Ectoderm / Q000196:embryology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D004707:Endoderm / Q000196:embryology; D005260:Female; D018392:Genomic Imprinting; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics; D014960:X Chromosome / Q000235:genetics; D049951:X Chromosome Inactivation
chemical_list: D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins