Publications

In response to various immune challenges, females show better survival than males; the X chromosome has an important role in this immunological advantage. X chromosome-linked diseases are usually restricted to males, who have only one copy of the X chromosome; however, females are more prone to autoimmune diseases, and the X chromosome may be involved in the breakdown of self tolerance. Several hypotheses have been proposed in recent years that ...

Reprogramming female mouse somatic cells into induced pluripotent stem cells (iPSCs) leads to X-chromosome reactivation. The extent to which increased X- chromosome dosage (X-dosage) in female iPSCs compared with male iPSCs leads to differences in the properties of iPSCs is still unclear. We show that chromatin accessibility in mouse iPSCs is modulated by X-dosage. Specific sets of transcriptional regulator motifs are enriched in chromatin with ...

BACKGROUND: Precise gene dosage of the X chromosomes is critical for normal development and cellular function. In mice, XX female somatic cells show transcriptional X chromosome upregulation of their single active X chromosome, while the other X chromosome is inactive. Moreover, the inactive X chromosome is reactivated during development in the inner cell mass and in germ cells through X chromosome reactivation, which can be studied in vitro by ...

In this thesis, I aimed to define the dynamics and the mechanisms that orchestrate the reversal of stable gene silencing during reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). I used X chromosome reactivation as a paradigm to better understand the reversal of silent chromatin. In addition, my goal was also to define the gene regulatory logic of mammalian pre- implantation development and reprogramming, as well as to ...

STUDY HYPOTHESIS:

Does a preferential X chromosome inactivation (XCI) pattern exist in female human pluripotent stem cells (hPSCs) and does the pattern change during long-term culture or upon differentiation?
STUDY FINDING:

We identified two independent phenomena that lead to aberrant XCI patterns in female hPSC: a rapid loss of histone H3 lysine 27 trimethylation (H3K27me3) and long non-coding X-inactive specific ...

In species with chromosomal sex determination, X chromosomes are predicted to evolve faster than autosomes because of positive selection on recessive alleles or weak purifying selection. We investigated X chromosome evolution in Stegodyphus spiders that differ in mating system, sex ratio, and population dynamics. We assigned scaffolds to X chromosomes and autosomes using a novel method based on flow cytometry of sperm cells and reduced ...

How the epigenome of one cell type is remodeled during reprogramming into another unrelated type of cell remains unclear. Overexpression of transcription factors in somatic cells enables the induction of induced pluripotent stem cells (iPSCs). This process entails genome-wide remodeling of DNA methylation, chromatin, and transcription. Recent work suggests that the number of active X chromosomes present in a cell influences remodeling of DNA ...

BACKGROUND:

Human pluripotent stem cells (hPSC), both embryonic and induced (hESC and hiPSC), are regarded as a valuable in vitro model for early human development. In order to fulfil this promise, it is important that these cells mimic as closely as possible the in vivo molecular events, both at the genetic and epigenetic level. One of the most important epigenetic events during early human development is X chromosome inactivation ...

BACKGROUND Male infertility is a worldwide problem, keeping many researchers puzzled. Besides environmental factors, much attention is paid to single gene defects. In this view, the sex chromosomes are particularly interesting since men only have a single copy of these chromosomes. The involvement of the Y chromosome in male infertility is obvious since the detection of Yq microdeletions. The role of the X chromosome, however, remains less ...

Dramatic epigenetic changes take place during mammalian differentiation from the naive pluripotent state including the silencing of one of the two X chromosomes in female cells through X chromosome inactivation. Conversely, reprogramming of somatic cells to naive pluripotency is coupled to X chromosome reactivation (XCR). Recent studies in the mouse system have shed light on the mechanisms of XCR by uncovering the timing and steps of XCR during ...