title: X-chromosome inactivation in monkey embryos and pluripotent stem cells.
abstract: Inactivation of one X chromosome in female mammals (XX) compensates for the reduced dosage of X-linked gene expression in males (XY). However, the inner cell mass (ICM) of mouse preimplantation blastocysts and their in vitro counterparts, pluripotent embryonic stem cells (ESCs), initially maintain two active X chromosomes (XaXa). Random X chromosome inactivation (XCI) takes place in the ICM lineage after implantation or upon differentiation of ESCs, resulting in mosaic tissues composed of two cell types carrying either maternal or paternal active X chromosomes. While the status of XCI in human embryos and ICMs remains unknown, majority of human female ESCs show non-random XCI. We demonstrate here that rhesus monkey ESCs also display monoallelic expression and methylation of X-linked genes in agreement with non-random XCI. However, XIST and other X-linked genes were expressed from both chromosomes in isolated female monkey ICMs indicating that ex vivo pluripotent cells retain XaXa. Intriguingly, the trophectoderm (TE) in preimplantation monkey blastocysts also expressed X-linked genes from both alleles suggesting that, unlike the mouse, primate TE lineage does not support imprinted paternal XCI. Our results provide insights into the species-specific nature of XCI in the primate system and reveal fundamental epigenetic differences between in vitro and ex vivo primate pluripotent cells.
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, 505 N.W. 185th Avenue, Beaverton, OR 97006, USA.
authors.forename: Masahito
authors.initials: M
authors.lastname: Tachibana
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Sparman
authors.forename: Hyo-Sang
authors.initials: HS
authors.lastname: Lee
authors.forename: Cathy M
authors.initials: CM
authors.lastname: Ramsey
authors.forename: Joy S
authors.initials: JS
authors.lastname: Woodward
authors.forename: Hathaitip
authors.initials: H
authors.lastname: Sritanaudomchai
authors.forename: Keith R
authors.initials: KR
authors.lastname: Masterson
authors.forename: Erin E
authors.initials: EE
authors.lastname: Wolff
authors.forename: Yibing
authors.initials: Y
authors.lastname: Jia
authors.forename: Shoukhrat M
authors.initials: SM
authors.lastname: Mitalipov
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D050172:Genes, X-Linked; D018392:Genomic Imprinting; D008253:Macaca mulatta; D008297:Male; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation