Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human

Takashima, Yasuhiro; Guo, Ge; Loos, Remco; Nichols, Jennifer; Ficz, Gabriella; Krueger, Felix; Oxley, David; Santos, Fátima; Clarke, James Stanier; Mansfield, William; Reik, Wolf; Bertone, Paul; Smith, Austin

doi:10.1016/j.cell.2015.06.052

Cited by 232 publications

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“…7), Esrra remains by far the most prevalent form expressed in hES cells, in contrast to murine ES cells. Nonetheless forced expression of Klf2 and Nanog in na€ ıve cells might result in somehow increased Esrrb in human pluripotent cells [183], although the absolute levels remain low (Fig. 7B).…”

Section: Concluding Remarks and Implications For The Derivation Of Namentioning

confidence: 99%

“…Counterintuitively, all na€ ıve hES cell lines derived so far lack robust expression of this TF. Reactivation of Esrrb expression has been claimed in different reports [184,185,190], or conversely the levels of Esrrb transcription have been interpreted as insufficient [182,183,191]. These discrepancies in interpretation can be resolved by comparing the relative levels of Esrrb and Esrra in mouse and human na€ ıve cells.…”

Section: Concluding Remarks and Implications For The Derivation Of Namentioning

confidence: 99%

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Esrrb, an estrogen‐related receptor involved in early development, pluripotency, and reprogramming

2017

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Estrogen-related receptor b (Esrrb) is part of a family of three orphan nuclear receptors with broad expression profiles and a generic function in regulating energy metabolism in mammals. However, Esrrb performs specific functions during early mouse development, in pluripotent and multipotent populations of the embryo as well as in primordial germ cells. Moreover, Esrrb also impinges upon the control of self-renewal in embryo-derived stem cells and enhances reprogramming. Here, we review the function of Esrrb with special emphasis on its role in pluripotency. Esrrb activity at crucial regulatory elements of the pluripotency network, coupled with its role as a mitotic bookmarking factor and the ability to reset cellular metabolism, might explain its potent functions in ensuring the stability of pluripotency and driving the late stages of reprogramming. Hence, we argue that Esrrb represents a key addition to the pantheon of transcription factors sustaining pluripotent stem cell identity in mice. Understanding the mechanisms governing the interplay between different estrogen-related receptors (ERRs) and their specificity of action may clarify the role these factors play during preimplantation development and in pluripotent cells in both mouse and humans.

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Section: Concluding Remarks and Implications For The Derivation Of Namentioning

confidence: 99%

Section: Concluding Remarks and Implications For The Derivation Of Namentioning

confidence: 99%

Esrrb, an estrogen‐related receptor involved in early development, pluripotency, and reprogramming

2017

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“…Faithful reprogramming requires establishment of the pluripotent methylome In contrast to the high levels of DNA methylation consistently observed in somatic cells, DNA methylation levels are low in the naïve pluripotent cells both in vivo Oswald et al, 2000;Smith et al, 2012Smith et al, , 2014Guo et al, 2014;Wang et al, 2014c) and in vitro (Ficz et al, 2013;Habibi et al, 2013;Leitch et al, 2013;Takashima et al, 2014). Considering this, it has been suggested that global DNA demethylation is a conserved and required feature of reprogramming events (Hill et al, 2014).…”

Section: Erasure and Remodelling Of Repressive Histone Modificationsmentioning

confidence: 99%

Reprogramming of cell fate: epigenetic memory and the erasure of memories past

2015

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Cell identity is a reflection of a cell type-specific gene expression profile, and consequently, cell type-specific transcription factor networks are considered to be at the heart of a given cellular phenotype. Although generally stable, cell identity can be reprogrammed in vitro by forced changes to the transcriptional network, the most dramatic example of which was shown by the induction of pluripotency in somatic cells by the ectopic expression of defined transcription factors alone. Although changes to cell fate can be achieved in this way, the efficiency of such conversion remains very low, in large part due to specific chromatin signatures constituting an epigenetic barrier to the transcription factor-mediated reprogramming processes. Here we discuss the two-way relationship between transcription factor binding and chromatin structure during cell fate reprogramming. We additionally explore the potential roles and mechanisms by which histone variants, chromatin remodelling enzymes, and histone and DNA modifications contribute to the stability of cell identity and/or provide a permissive environment for cell fate change during cellular reprogramming.

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“…These differences have been attributed to ESCs being in a developmentally more advanced, "primed" state, compared to the "naïve" state of pluripotency found in mouse ESCs and in the cells from human blastocysts [135]. By using specific culture conditions, it is possible to alter the cell state of hESCs in a way that they more closely resemble naïve pluripotent cells [136][137][138][139][140]. Strikingly, ERVs were found to be a key indicator for these alternative states of pluripotency ( Fig 3A).…”

Section: Ervs As Markers Of Cell Identity and Cell Potencymentioning

confidence: 99%

CTRL+INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome

Göke

2016

EMBO Reports

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The human genome contains millions of fragments from retrotransposons-highly repetitive DNA sequences that were once able to "copy and paste" themselves to other regions in the genome. However, the majority of retrotransposons have lost this capacity through acquisition of mutations or through endogenous silencing mechanisms. Without this imminent threat of transposition, retrotransposons have the potential to act as a major source of genomic innovation. Indeed, large numbers of retrotransposons have been found to be active in specific contexts: as gene regulatory elements and promoters for protein-coding genes or long noncoding RNAs, among others. In this review, we summarise recent findings about retrotransposons, with implications in gene expression regulation, the expansion of gene isoform diversity and the generation of long noncoding RNAs. We highlight key examples that demonstrate their role in cellular identity and their versatility as markers of cell states, and we discuss how their dysregulation may contribute to the formation of and possibly therapeutic response in human cancers.

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Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human

Cited by 232 publications

References 0 publications

Esrrb, an estrogen‐related receptor involved in early development, pluripotency, and reprogramming

Esrrb, an estrogen‐related receptor involved in early development, pluripotency, and reprogramming

Reprogramming of cell fate: epigenetic memory and the erasure of memories past

CTRL+INSERT: retrotransposons and their contribution to regulation and innovation of the transcriptome

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