New Insights into X-Chromosome Reactivation during Reprogramming to Pluripotency

Panda, Amitesh; Ż̷ylicz, J.; Pasque, Vincent

doi:10.3390/cells9122706

Cited by 14 publications

(14 citation statements)

References 218 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once established, XCI is mitotically heritable, i.e., daughter cells have the same inactive X as their mother cell, so choice is propagated and skewed spatial patterns maintained. The reactivation of the inactive X chromosome can happen spontaneously (though very rarely), in pathological contexts or in specific developmental moments, such as in the cells that will produce the embryo proper in mice or during oogenesis-reviewed in [125,[161][162][163].…”

Section: Choice: the Second Most Important Moment In The Lives Of XX ...mentioning

confidence: 99%

Mechanisms of Choice in X-Chromosome Inactivation

Furlan

Galupa

2022

Cells

View full text Add to dashboard Cite

Early in development, placental and marsupial mammals harbouring at least two X chromosomes per nucleus are faced with a choice that affects the rest of their lives: which of those X chromosomes to transcriptionally inactivate. This choice underlies phenotypical diversity in the composition of tissues and organs and in their response to the environment, and can determine whether an individual will be healthy or affected by an X-linked disease. Here, we review our current understanding of the process of choice during X-chromosome inactivation and its implications, focusing on the strategies evolved by different mammalian lineages and on the known and unknown molecular mechanisms and players involved.

show abstract

Section: Choice: the Second Most Important Moment In The Lives Of XX ...mentioning

confidence: 99%

Mechanisms of Choice in X-Chromosome Inactivation

Furlan

Galupa

2022

Cells

View full text Add to dashboard Cite

show abstract

“…MAPK signaling is known to be inhibited by double X-dosage (Schulz et al, 2014;Song et al, 2019;Genolet et al, 2021), which might explain enrichment of this pathway in our XGFP-PGCLCs. LIF signaling on the other hand, which is enriched in our XGFP+ PGCLCs, is known to enable expression of the naive pluripotency network, which represses Xist, thereby promoting the active X state (Payer & Lee, 2014;Panda et al, 2020). Furthermore, enrichment for meiotic cell cycle genes in XGFP+ PGCLCs such as Aurkc, Dazl and Piwil2, suggests a premature activation of a subset of meiotic genes in XGFP+ PGCLCs.…”

Section: Xgfp+ and Xgfp-pgclcs Define Distinct Subpopulationsmentioning

confidence: 97%

A temporally controlled sequence of X-chromosome inactivation and reactivation defines female mouse in vitro germ cells with meiotic potential

Severino

Bauer

Mattimoe

et al. 2021

Preprint

View full text Add to dashboard Cite

The early mammalian germ cell lineage is characterized by extensive epigenetic reprogramming, which is required for the maturation into functional eggs and sperm. In particular, the epigenome needs to be reset before parental marks can be established and then transmitted to the next generation. In the female germ line, reactivation of the inactive X chromosome is one of the most prominent epigenetic reprogramming events, and despite its scale involving an entire chromosome affecting hundreds of genes, very little is known about its kinetics and biological function. Here we investigate X-chromosome inactivation and reactivation dynamics by employing a tailor-made in vitro system to visualize the X-status during differentiation of primordial germ cell-like cells (PGCLCs) from female mouse embryonic stem cells (ESCs). We find that the degree of X-inactivation in PGCLCs is moderate when compared to somatic cells and characterized by a large number of genes escaping full inactivation. Nevertheless, PGCLCs that fail to undergo X-inactivation show an abnormal gene expression signature and deficiencies in meiotic entry. Subsequent to X-inactivation we observe gradual step-wise X-reactivation, which is mostly completed by the end of meiotic prophase I. Cells deviating from these progressive kinetics and undergoing X-reactivation too rapidly fail to enter a meiotic trajectory. Our data reveals that a fine-tuned X-inactivation and -reactivation cycle is a critical feature of female germ cell developmental competence towards meiosis and oogenesis

show abstract

“…Chromosome-wide gene silencing from the inactive X chromosome (Xi) in mammalian cells is erased in a process known as X chromosome reactivation (XCR), which has emerged as a paradigm for studying chromatin, gene regulation, development, pluripotency, and reprogramming [38,39]. In mice, humans and marsupials, XCR takes place in vivo in female primordial germ cells (PGCs) [35,40,41], and in the naive mouse epiblast, with the exception of marsupials where XCR does not take place in the epiblast [14].…”

Section: Introductionmentioning

confidence: 99%

“…Pluripotency TFs have recently been implicated as factors mediating chromosomewide XCR [39,47,49]. Pluripotency is strongly linked to XCR in mice and humans but not in marsupials, suggesting that placental mammals have evolved molecular mechanisms to couple naive pluripotency with XCR [14,50].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

et al. 2021

Self Cite

View full text Add to dashboard Cite

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 reprogramming of somatic cells to pluripotency. How chromatin processes and gene regulatory networks evolved to regulate X chromosome dosage in the somatic state and during X chromosome reactivation remains unclear. Results Using genome-wide approaches, allele-specific ATAC-seq and single-cell RNA-seq, in female embryonic fibroblasts and during reprogramming to pluripotency, we show that chromatin accessibility on the upregulated mammalian active X chromosome is increased compared to autosomes. We further show that increased accessibility on the active X chromosome is erased by reprogramming, accompanied by erasure of transcriptional X chromosome upregulation and the loss of increased transcriptional burst frequency. In addition, we characterize gene regulatory networks during reprogramming and X chromosome reactivation, revealing changes in regulatory states. Our data show that ZFP42/REX1, a pluripotency-associated gene that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency. Conclusions Our data reveal the existence of intrinsic compensatory mechanisms that involve modulation of chromatin accessibility to counteract X-to-Autosome gene dosage imbalances caused by evolutionary or in vitro X chromosome loss and X chromosome inactivation in mammalian cells.

show abstract

New Insights into X-Chromosome Reactivation during Reprogramming to Pluripotency

Cited by 14 publications

References 218 publications

Mechanisms of Choice in X-Chromosome Inactivation

Mechanisms of Choice in X-Chromosome Inactivation

A temporally controlled sequence of X-chromosome inactivation and reactivation defines female mouse in vitro germ cells with meiotic potential

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

Contact Info

Product

Resources

About