X-Chromosome Inactivation during Preimplantation Development and in Pluripotent Stem Cells

Abstract

X dosage compensation between XX female and XY male mammalian cells is achieved by a process known as X-chromosome inactivation (XCI). XCI initiates early during preimplantation development in female cells, and it is subsequently stably maintained in somatic cells. However, XCI is a reversible process that occurs in vivo in the inner cell mass of the blastocyst, in primordial germ cells or in spermatids during reprogramming. Erasure of transcriptional gene silencing can occur though a mechanism named X-chromosome reactivation (XCR). XCI and XCR have been substantially deciphered in the mouse, whereas they still remain debated in the human. In this review, we summarized the recent advances in the knowledge of X-linked gene dosage compensation during mouse and human preimplantation development and in pluripotent stem cells.

Dysregulated Gene Expression of Imprinted and X-Linked Genes: A Link to Poor Development of Bovine Haploid Androgenetic Embryos

“…Silencing of one of the X chromosomes in biparental female embryos is regulated by the expression of XIST, a non-coding RNA that acts as a major effector on X chromosome inactivation (XCI), and the methylation of XIST prevents its expression. In the mouse, following zygotic genome activation (ZGA), only the paternal X chromosome (Xp) undergoes Xist-mediated silencing (Xip), which is maintained in the trophectoderm at the blastocyst stage, but in epiblast cells the inactive Xp is reactivated and later, upon implantation, epiblast cells undergo random XCI (Rebuzzini et al, 2020). However, the pattern of XCI in other mammalian species is not clear yet.…”

Dosage Compensation in Females with X-Linked Metabolic Disorders

“… Model of X chromosome inactivation (XCI) in female human early development [ 14 , 15 ]. Female zygote inherits active maternal and paternal X chromosomes (Xm and Xp, respectively).…”

Building Pluripotency Identity in the Early Embryo and Derived Stem Cells

“…During pre-implantation development, the establishment of the totipotency condition and the following transition towards pluripotency is accompanied by another important epigenetic event, which occurs only in the female pre-implantation embryos, i.e., the X chromosome inactivation (XCI). Although with different dynamics in mouse and human [140], the XCI compensatory mechanism is mediated by the expression of the long non-coding RNA (lncRNA) Xist (see Section 3.2.2 Long non-coding RNAs), through which one of the two female X chromosomes (paternal X (Xp); maternal X (Xm)) is randomly inactivated to equalize X-linked gene expression between male and female individuals [141]. Opposite to XCI, reactivation of the Xi chromosome, leading to an Xa, occurs only in the mouse female embryos.…”

“…It co-accumulates with XIST, controlling the association of XIST to the putative Xi in cis, possibly to antagonize or temper its silencing ability [184]. In mouse and human peri-implantation embryos, several other lncRNAs (e.g., Tsix, Jpx, Xite, Ftx and Tsx, for mouse; TSIX, JPX and FTX, for human) concur with XIST in the silencing process [140].…”