X chromosome reactivation in reprogramming and in development

Pasque, Vincent; Plath, Kathrin

doi:10.1016/j.ceb.2015.10.006

Cited by 56 publications

(62 citation statements)

References 87 publications

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“…For more detailed mechanistic studies, embryonic stem cells from these species will be valuable model systems. The use of human ESCs for studying X-dosage-dependent effects has so far been hampered by the fact that most cell lines adopt a state where one X-chromosome is at least partially silenced [54]. A recent study has characterized the X-inactivation status and the differentiation potential of a series of female human ESC lines in detail [55].…”

Section: (F ) Zfxmentioning

confidence: 99%

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

Schulz

2017

Phil. Trans. R. Soc. B

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Already during early embryogenesis, before sex-specific hormone production is initiated, sex differences in embryonic development have been observed in several mammalian species. Typically, female embryos develop more slowly than their male siblings. A similar phenotype has recently been described in differentiating murine embryonic stem cells, where a double dose of the X-chromosome halts differentiation until dosage-compensation has been achieved through X-chromosome inactivation. On the molecular level, several processes associated with early differentiation of embryonic stem cells have been found to be affected by X-chromosome dosage, such as the transcriptional state of the pluripotency network, the activity pattern of several signal transduction pathways and global levels of DNA-methylation. This review provides an overview of the sex differences described in embryonic stem cells from mice and discusses a series of X-linked genes that are associated with pluripotency, signalling and differentiation and their potential involvement in mediating the observed X-dosage–dependent effects. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

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Section: (F ) Zfxmentioning

confidence: 99%

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

Schulz

2017

Phil. Trans. R. Soc. B

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“…In contrast, these two stem cell types show different epigenetic states of X chromosomes; XCR occurs in ESCs, whereas XCI occurs in EpiSCs. Thus, reactivation of X chromosomes is used as an indicator of naïve-state PSCs (Ohhata and Wutz, 2013;Pasque and Plath, 2015). However, currently there is no means of monitoring XCR in living cells.…”

Section: Introductionmentioning

confidence: 99%

“…Such XCR is also observed during the genomic reprogramming of induced pluripotent stem cells (iPSCs) derived from differentiated cells. Thus, inactivation and reactivation of the X chromosomes are closely linked to the loss and gain of pluripotency, respectively (Pasque and Plath, 2015).…”

Section: Introductionmentioning

confidence: 99%

Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells

et al. 2016

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Pluripotent stem cells can be classified into two distinct states, naïve and primed, which show different degrees of potency. One difficulty in stem cell research is the inability to distinguish these states in live cells. Studies on female mice have shown that reactivation of inactive X chromosomes occurs in the naïve state, while one of the X chromosomes is inactivated in the primed state. Therefore, we aimed to distinguish the two states by monitoring X chromosome reactivation. Thus far, X chromosome reactivation has been analysed using fixed cells; here, we inserted different fluorescent reporter gene cassettes (mCherry and eGFP) into each X chromosome. Using these knock-in 'Momiji' mice, we detected X chromosome reactivation accurately in live embryos, and confirmed that the pluripotent states of embryos were stable ex vivo, as represented by embryonic and epiblast stem cells in terms of X chromosome reactivation. Thus, Momiji mice provide a simple and accurate method for identifying stem cell status based on X chromosome reactivation.

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“…Then, one X chromosome is randomly inactivated for dosage compensation after exit from the ICM state. [28][29][30] This dynamic epigenetic regulation plays an important role in normal mammalian development.…”

Section: Epigenetic Reprogramming and Programming In Mouse Early Devementioning

confidence: 99%

Epigenetic foundations of pluripotent stem cells that recapitulate in vivo pluripotency

Yagi

Yamanaka

Yamada

2017

Laboratory Investigation

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In mammalian development, dynamic epigenetic reprogramming occurs in pre-implantation embryos and primordial germ cells and plays a critical role in conferring pluripotency on embryonic cells. Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been derived and maintained in vitro under culture conditions that include stimulators and inhibitors of extrinsic signaling. Recent advances in stem cell cultivation have opened the possibility of capturing naive pluripotency, which is reminiscent of the pluripotency of inner cell mass cells, in vitro. However, emerging evidence has revealed complexity of epigenetic regulation in pluripotent stem cells in vitro that reflects the developmental stage, gender, and species. In this review, we describe the developmental potential and epigenetic regulation of pluripotent stem cells in rodents and humans in vitro and discuss unsolved issues in developing strategies to capture in vivo pluripotency in vitro.

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X chromosome reactivation in reprogramming and in development

Cited by 56 publications

References 87 publications

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

X-chromosome dosage as a modulator of pluripotency, signalling and differentiation?

Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells

Epigenetic foundations of pluripotent stem cells that recapitulate in vivo pluripotency

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