X Chromosome Reactivation Dynamics Reveal Stages of Reprogramming to Pluripotency

Pasque, Vincent; Tchieu, Jason; Karnik, Rahul; Uyeda, Molly Javier; Dimashkie, Anupama; Case, Dana; Papp, Bernadett; Bonora, Giancarlo; Patel, Sanjeet G.; Ho, Ritchie; Schmidt, Ryan; McKee, Robin; Sado, Takashi; Tada, Takashi; Meissner, Alexander; Plath, Kathrin

doi:10.1016/j.cell.2014.11.040

Cited by 102 publications

(237 citation statements)

References 59 publications

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“…A recent study dissected the kinetics of X-chromosome reactivation during the reprogramming of MEFs (Pasque et al, 2014). After the transduction of reprogramming factors into MEFs, the Xi colocalizes with EZH2, an enzyme of the Polycomb-group family that leads to chromatin condensation by the addition of three methyl groups to lysine 27 of histone 3 (H3K27me3).…”

Section: X-chromosome Activitymentioning

confidence: 99%

A developmental framework for induced pluripotency

2015

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During development, cells transition from a pluripotent to a differentiated state, generating all the different types of cells in the body. Development is generally considered an irreversible process, meaning that a differentiated cell is thought to be unable to return to the pluripotent state. However, it is now possible to reprogram mature cells to pluripotency. It is generally thought that reprogramming is accomplished by reversing the natural developmental differentiation process, suggesting that the two mechanisms are closely related. Therefore, a detailed study of cell reprogramming has the potential to shed light on unexplained developmental mechanisms and, conversely, a better understanding of developmental differentiation can help improve cell reprogramming. However, fundamental differences between reprogramming processes and multi-lineage specification during early embryonic development have also been uncovered. In addition, there are multiple routes by which differentiated cells can re-enter the pluripotent state. In this Review, we discuss the connections and disparities between differentiation and reprogramming, and assess the degree to which reprogramming can be considered as a simple reversal of development.

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Section: X-chromosome Activitymentioning

confidence: 99%

A developmental framework for induced pluripotency

2015

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“…This likely reflects an intermediate reprogramming stage and mirrors the global increase in nuclear PRC2 and H3K27me3 as also seen in XCR--competent cells in vivo, like in the epiblast and in PGCs [127,128]. Later however, after Xist gets downregulated, the H3K27me3 mark is erased from the Xi during XCR [126]. These steps occur approximately at the time, when endogenous pluripotency genes like Nanog become reactivated [47,125,126].…”

Section: Resetting the Xci--stage By X--chromosome Reactivation (Xcr)mentioning

confidence: 99%

“…During iPSC generation, XCR seems to be a gradual, late event [125,126]. This might be due to the fact that like in PGCs, random XCI has to be reversed in iPSCs.…”

Section: Resetting the Xci--stage By X--chromosome Reactivation (Xcr)mentioning

confidence: 99%

“…Later however, after Xist gets downregulated, the H3K27me3 mark is erased from the Xi during XCR [126]. These steps occur approximately at the time, when endogenous pluripotency genes like Nanog become reactivated [47,125,126]. Xist is repressed both directly and indirectly by binding of pluripotency factors like NANOG or PRDM14 to Xist intron 1 and the promoter of the Xist--activator Rnf12 [47,79,89].…”

Section: Resetting the Xci--stage By X--chromosome Reactivation (Xcr)mentioning

confidence: 99%

“…XCR in iPSCs involves multiple steps, of which some occur in reverse order to the XCI process, while others follow a different kinetics [126]. One of the earliest events during iPSC reprogramming is an initial enrichment of the PRC2 complex and its associated H3K27me3 mark on the Xi.…”

Section: Resetting the Xci--stage By X--chromosome Reactivation (Xcr)mentioning

confidence: 99%

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Developmental regulation of X-chromosome inactivation

Payer

2016

Seminars in Cell & Developmental Biology

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With the emergence of sex--determination by sex chromosomes, which differ in composition and number between males and females, appeared the need to equalize X--chromosomal gene dosage between the sexes. Mammals have devised the strategy of X--chromosome inactivation (XCI), in which one of the two X--chromosomes is rendered transcriptionally silent in females. In the mouse, the best--studied model organism with respect to XCI, this inactivation process occurs in different forms, imprinted and random, interspersed by periods of X--chromosome reactivation (XCR), which is needed to switch between the different modes of XCI. In this review, I describe the recent advances with respect to the developmental control of XCI and XCR and in particular their link to differentiation and pluripotency. Furthermore, I review the mechanisms, which influence the timing and choice, with which one of the two X--chromosomes is chosen for inactivation during random XCI. This has an impact on how females are mosaics with regard to which X--chromosome is active in different cells, which has implications on the severity of diseases caused by X--linked mutations.

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Mechanisms underlying the formation of induced pluripotent stem cells

González

Huangfu

2015

WIREs Developmental Biology

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Human pluripotent stem cells (hPSCs) offer unique opportunities for studying human biology, modeling diseases and for therapeutic applications. The simplest approach so far to generate human PSCs lines is through reprogramming of somatic cells from an individual by defined factors, referred to simply as reprogramming. Reprogramming circumvents the ethical issues associated with human embryonic stem cells (hESCs) and nuclear transfer hESCs (nt-hESCs), and the resulting induced pluripotent stem cells (hiPSCs) retain the same basic genetic makeup as the somatic cell used for reprogramming. Since the first report of iPSCs by Takahashi and Yamanaka, the molecular mechanisms of reprogramming have been extensively investigated. A better mechanistic understanding of reprogramming is fundamental not only to iPSC biology and improving the quality of iPSCs for therapeutic use, but also to our understanding of the molecular basis of cell identity, pluripotency and plasticity. Here we summarize the genetic, epigenetic and cellular events during reprogramming, and the roles of various factors identified thus far in the reprogramming process.

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X Chromosome Reactivation Dynamics Reveal Stages of Reprogramming to Pluripotency

Cited by 102 publications

References 59 publications

A developmental framework for induced pluripotency

A developmental framework for induced pluripotency

Developmental regulation of X-chromosome inactivation

Mechanisms underlying the formation of induced pluripotent stem cells

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