title: Single-Cell XIST Expression in Human Preimplantation Embryos and Newly Reprogrammed Female Induced Pluripotent Stem Cells.
abstract: The process of X chromosome inactivation (XCI) during reprogramming to produce human induced pluripotent stem cells (iPSCs), as well as during the extensive programming that occurs in human preimplantation development, is not well-understood. Indeed, studies of XCI during reprogramming to iPSCs report cells with two active X chromosomes and/or cells with one inactive X chromosome. Here, we examine expression of the long noncoding RNA, XIST, in single cells of human embryos through the oocyte-to-embryo transition and in new mRNA reprogrammed iPSCs. We show that XIST is first expressed beginning at the 4-cell stage, coincident with the onset of embryonic genome activation in an asynchronous manner. Additionally, we report that mRNA reprogramming produces iPSCs that initially express XIST transcript; however, expression is rapidly lost with culture. Loss of XIST and H3K27me3 enrichment at the inactive X chromosome at late passage results in X chromosome expression changes. Our data may contribute to applications in disease modeling and potential translational applications of female stem cells.
authors.affiliation: Department of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Briggs
authors.affiliation: Department of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
authors.forename: Antonia A
authors.initials: AA
authors.lastname: Dominguez
authors.affiliation: Department of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
authors.forename: Shawn L
authors.initials: SL
authors.lastname: Chavez
authors.affiliation: Department of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.|Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
authors.forename: Renee A
authors.initials: RA
authors.lastname: Reijo Pera
mesh_terms: D001755:Blastocyst / Q000166:cytology*; D065150:Cellular Reprogramming / Q000235:genetics*; D005260:Female; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D049951:X Chromosome Inactivation / Q000235:genetics*
keywords: Human; Human induced pluripotent stem cells; Preimplantation embryo development; X chromosome inactivation; XIST RNA