DNA (De)Methylation: The Passive Route to Naïvety?

Leitch, Harry G.; Surani, M. Azim; Hájková, Petra

doi:10.1016/j.tig.2016.08.005

Cited by 5 publications

(2 citation statements)

References 16 publications

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“…GSEA enrichment results showed that, in the high ECM score group, the most hypomethylated biological processes were synapse development and cell differentiation, which may lead to EMT and cell stemness, and the most hypermethylated biological processes were less significant to be mentioned ( Figure 3I ). Global hypomethylation is an important feature of naïve pluripotent cells and complex regulation of the epigenome also promotes CSCs formation ( 39 , 40 ). Therefore, we speculated that ECM deposition might promote CSC formation through an epigenetic mechanism.…”

Section: Resultsmentioning

confidence: 99%

Extracellular Matrix Characterization in Gastric Cancer Helps to Predict Prognosis and Chemotherapy Response

Yang

Xue

et al. 2021

Front. Oncol.

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The extracellular matrix (ECM) plays a central role in the formation of the tumor microenvironment. The deposition of the ECM is associated with poor prognosis in a variety of tumors. Aberrant ECM deposition could undermine the effect of chemotherapy and immunotherapy. However, there is no systematic analysis on the relationship between the ECM and prognosis or chemotherapy effect. In the present study, we applied the gene set variation analysis (GSVA) algorithm to score 2199 canonical pathways in 2125 cases of probe or sequencing data and identified the core matrisome as the driving factor in gastric cancer progression. We classified gastric cancer samples into three clusters according to the composition of the ECM and evaluated clinical and multi-omics characterization of ECM phenotypes. The ECM score was evaluated by GSVA score of core matrisome and a higher ECM score predicted poor prognosis of gastric cancer [Hazard Ratio (HR), 2.084; p-value < 2 × 10−16]. In The Cancer Genome Atlas (TCGA) cohort and KUGH, YUSH, and KUCM cohorts, we verified that patients with a low ECM score could benefit from chemotherapy. By contrast, patients with a high ECM score did not achieve satisfactory response from chemotherapy. Determining the characteristics of the ECM microenvironment might help to predict the prognosis and chemotherapy response of patients with gastric cancer, and help to resolve the enigma of chemoresistance acquisition, as well as providing inspiration to develop combination therapy.

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Section: Resultsmentioning

confidence: 99%

Extracellular Matrix Characterization in Gastric Cancer Helps to Predict Prognosis and Chemotherapy Response

Yang

Xue

et al. 2021

Front. Oncol.

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“…In mice, the ICM and epiblast cells of blastocysts, as well as the embryonic stem (ES) cell lines that are derived from them, are in the naive state. Naive pluripotency is associated with the expression of transcription factors Klf2, Klf4, Gbx2, Tfcp2l1, Esrrb, Tbx3, and Sall4 (Dunn et al, 2014), low DNA methylation (Leitch et al, 2013; Leitch et al, 2016), high mitochondrial respiration (Carbognin et al, 2016; Sone et al, 2017), and enrichment of active histone modifications at promoter regions of developmental genes (Hayashi et al, 2008). Formative pluripotency characterizes the epiblast cells of peri-implantation embryos, as well as the corresponding pluripotent stem cell lines, called formative stem (FS) cells (Kinoshita et al, 2020; Smith, 2017).…”

Section: Introductionmentioning

confidence: 99%

Major transcriptomic, epigenetic and metabolic changes underly the pluripotency continuum in rabbit preimplantation embryos

Bouchereau

Jouneau

Archilla

et al. 2021

Preprint

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Despite the growing interest in the rabbit model for developmental and stem cell biology, the characterization of embryos at the molecular level is still poorly documented. We conducted a transcriptome analysis of rabbit pre-implantation embryos from E2.7 (morula stage) to E6.6 (early primitive streak stage) using bulk and single-cell RNA-sequencing, and single-cell Biomark qPCR. In parallel, we studied oxidative phosphorylation and glycolysis and analyzed active and repressive epigenetic modifications during blastocyst formation and expansion. We generated a transcriptomic, epigenetic, and metabolic map of the pluripotency continuum in rabbit preimplantation embryos and identified novel markers of naive pluripotency that might be instrumental for deriving naive pluripotent stem cell lines. Although the rabbit is evolutionarily closer to mice than to primates, we found that the transcriptome of rabbit epiblast cells shares common features with that of humans and non-human primates.

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The Epigenetic Paradox of Pluripotent ES Cells

Festuccia

González

Navarro

2017

Journal of Molecular Biology

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The propagation and maintenance of gene expression programs are at the foundation of the preservation of cell identity. A large and complex set of epigenetic mechanisms enables the long-term stability and inheritance of transcription states. A key property of authentic epigenetic regulation is being independent from the instructive signals used for its establishment. This makes epigenetic regulation, particularly epigenetic silencing, extremely robust and powerful to lock regulatory states and stabilise cell identity. In line with this, the establishment of epigenetic silencing during development restricts cell potency and maintains the cell fate choices made by transcription factors (TFs). However, how more immature cells that have not yet established their definitive fate maintain their transitory identity without compromising their responsiveness to signalling cues remains unclear. A paradigmatic example is provided by pluripotent embryonic stem (ES) cells derived from a transient population of cells of the blastocyst. Here, we argue that ES cells represent an interesting "epigenetic paradox": even though they are captured in a self-renewing state characterised by extremely efficient maintenance of their identity, which is a typical manifestation of robust epigenetic regulation, they seem not to heavily rely on classical epigenetic mechanisms. Indeed, self-renewal strictly depends on the TFs that previously instructed their undifferentiated identity and relies on a particular signalling-dependent chromatin state where repressive chromatin marks play minor roles. Although this "epigenetic paradox" may underlie their exquisite responsiveness to developmental cues, it suggests that alternative mechanisms to faithfully propagate gene regulatory states might be prevalent in ES cells.

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DNA (De)Methylation: The Passive Route to Naïvety?

Cited by 5 publications

References 16 publications

Extracellular Matrix Characterization in Gastric Cancer Helps to Predict Prognosis and Chemotherapy Response

Extracellular Matrix Characterization in Gastric Cancer Helps to Predict Prognosis and Chemotherapy Response

Major transcriptomic, epigenetic and metabolic changes underly the pluripotency continuum in rabbit preimplantation embryos

The Epigenetic Paradox of Pluripotent ES Cells

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