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.
Original language | English (US) |
---|---|
Pages (from-to) | 1771-1781 |
Number of pages | 11 |
Journal | Stem Cells |
Volume | 33 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1 2015 |
Externally published | Yes |
Keywords
- Human
- Human induced pluripotent stem cells
- Preimplantation embryo development
- X chromosome inactivation
- XIST RNA
ASJC Scopus subject areas
- Molecular Medicine
- Developmental Biology
- Cell Biology