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Genomic integrity safeguards pluripotency in embryonic stem cells

ABSTRACT: Genomic integrity safeguards pluripotency in embryonic stem cells

PROVIDER: PRJNA438830 | ENA |

REPOSITORIES: ENA

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Genomic integrity safeguards pluripotency in embryonic stem cells

Project description:Illumina BeadChip array analyses of mouse embryonic stem cell gene expression profiles in the presence of or upon knockdown of 4 candidate factors regulating genomic integrity -- Chek1, Ppm1g, Ppp2r1b and Bub1b. An ES complementation 'rescue' system was employed to measure the effects of knockdown (minus Dox). The 4 candidate factors are rescued to wildtype levels in the presence of Dox (plus Dox). A control rescue ES cell line, with a Luciferase-targeting shRNA, was also assessed.

2018-11-01 | GSE111982 | GEO

Transcriptional repressor FOXD3 safeguards genome integrity in embryonic stem cells

Project description:Transcriptional repressor FOXD3 safeguards genome integrity in embryonic stem cells

| PRJNA760536 | ENA

Genomic Integrity Safeguards Self-Renewal in Embryonic Stem Cells.

Project description:A multitude of signals are coordinated to maintain self-renewal in embryonic stem cells (ESCs). To unravel the essential internal and external signals required for sustaining the ESC state, we expand upon a set of ESC pluripotency-associated phosphoregulators (PRs) identified previously by short hairpin RNA (shRNA) screening. In addition to the previously described Aurka, we identify 4 additional PRs (Bub1b, Chek1, Ppm1g, and Ppp2r1b) whose depletion compromises self-renewal and leads to consequent differentiation. Global gene expression profiling and computational analyses reveal that knockdown of the 5 PRs leads to DNA damage/genome instability, activating p53 and culminating in ESC differentiation. Similarly, depletion of genome integrity-associated genes involved in DNA replication and checkpoint, mRNA processing, and Charcot-Marie-Tooth disease lead to compromise of ESC self-renewal via an increase in p53 activity. Our studies demonstrate an essential link between genomic integrity and developmental cell fate regulation in ESCs.

| S-EPMC6708277 | biostudies-literature

TET activity safeguards pluripotency throughout embryonic dormancy.

Project description:Dormancy is an essential biological process for the propagation of many life forms through generations and stressful conditions. Early embryos of many mammals are preservable for weeks to months within the uterus in a dormant state called diapause, which can be induced in vitro through mTOR inhibition. Cellular strategies that safeguard original cell identity within the silent genomic landscape of dormancy are not known. Here we show that the protection of cis-regulatory elements from silencing is key to maintaining pluripotency in the dormant state. We reveal a TET-transcription factor axis, in which TET-mediated DNA demethylation and recruitment of methylation-sensitive transcription factor TFE3 drive transcriptionally inert chromatin adaptations during dormancy transition. Perturbation of TET activity compromises pluripotency and survival of mouse embryos under dormancy, whereas its enhancement improves survival rates. Our results reveal an essential mechanism for propagating the cellular identity of dormant cells, with implications for regeneration and disease.

| S-EPMC11479945 | biostudies-literature

BEND3 safeguards pluripotency by repressing differentiation-associated genes

Project description:BEND3 safeguards pluripotency by repressing differentiation-associated genes

| PRJNA718308 | ENA

JAK2-CHK2 signaling safeguards the integrity of the mitotic spindle assembly checkpoint and genome stability

Project description:This dataset consists of 1 raw MS file and associated peak list and result file, acquired on an Orbitrap Elite mass spectrometer operated in Data Dependent Acquisition mode. The files are associated with a manuscript submitted for publication. Publication title: "JAK2-CHK2 signaling safeguards the integrity of the mitotic spindle assembly checkpoint and genome stability"

2021-03-31 | MSV000087138 | MassIVE

Tracking the embryonic stem cell transition from ground state pluripotency

Project description:Mouse embryonic stem (ES) cells are locked into self-renewal by shielding from inductive cues. Release from this ground state in minimal conditions offers a system for delineating developmental progression from naive pluripotency. Here we examined the initial transition process. The ES cell population behaves asynchronously. We therefore exploited a short-half-life Rex1::GFP reporter to isolate cells either side of exit from naive status. Differentiation of Rex1-GFPd2 ES cells was initiated by withdrawing 2i (Kalkan et al., 2016). Undifferentiated 2i-cells and post-2i withdrawal differentiating populations (16h, 25h-Rex1-High, 25h-Rex1-Low) were subjected to proteomic analysis by Mass Spectrometry.

2017-02-22 | PXD005581 | Pride

The totipotent 2C-like state safeguards genomic stability of mouse embryonic stem cells

Project description:The totipotent 2C-like state safeguards genomic stability of mouse embryonic stem cells

| PRJNA1059497 | ENA

LncPRESS1 is a p53-regulated lncRNA that safeguards pluripotency by disrupting SIRT6 mediated de-acetylation of histone H3K56

Project description:Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs, highly expressed in pluripotent hESCs and repressed by p53 during differentiation, to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors. RNA-seq of hESCs depleted of lncPRESS1 revealed that lncPRESS1 controls a gene network that promotes pluripotency. Further, we found that lncPRESS1 physically interacts with SIRT6 to prevent SIRT6 chromatin localization and maintain high levels of histone H3K56 and H3K9 acetylation at promoters of pluripotency genes. In summary, we describe a novel pluripotency-specific lncRNA that safeguards the hESC state by disrupting SIRT6 activity

2016-12-07 | GSE76023 | GEO

An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming

Project description:This SuperSeries is composed of the following subset Series: GSE30995: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [RNA-Seq] GSE31006: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [ChIP-Seq] GSE31007: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [protein binding microarray] GSE31948: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [AS microarray] Refer to individual Series

2011-09-14 | E-GEOD-30992 | biostudies-arrayexpress

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