Single‐Cell XIST Expression in Human Preimplantation Embryos and Newly Reprogrammed Female Induced Pluripotent Stem Cells

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 repo...

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Published inStem cells (Dayton, Ohio) Vol. 33; no. 6; pp. 1771 - 1781
Main Authors Briggs, Sharon F., Dominguez, Antonia A., Chavez, Shawn L., Reijo Pera, Renee A.
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.06.2015
John Wiley and Sons Inc
Subjects
Blastocyst - cytology
Cellular Reprogramming - genetics
Chromosomes
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Embryos
Female
Human
Human Embryonic Stem Cells - cytology
Human induced pluripotent stem cells
Humans
Induced Pluripotent Stem Cells - cytology
Preimplantation embryo development
Stem cells
X chromosome inactivation
X Chromosome Inactivation - genetics
XIST RNA
Human
Human induced pluripotent stem cells
Preimplantation embryo development
X chromosome inactivation
XIST RNA
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Summary: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. Stem Cells 2015;33:1771–1781
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ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1992