Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Apoptosis and differentiation commitment:novel insights revealed by gene profiling studies in mouse Embryonic Stem cells

ABSTRACT: Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in presence of Leukaemia Inhibitory Factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38a MAP kinase activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD 169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at three days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene which prevents apoptosis of early differentiated cells. Keywords: mouse ES cells; apoptosis; differentiation; p38; PD169316; Ca++ binding proteins; Metallothionein; stress-response Keywords: ordered

ORGANISM(S): Mus musculus

PROVIDER: GSE2042 | GEO | 2005/12/21

SECONDARY ACCESSION(S): PRJNA91871

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of mouse embryonic stem cells (ES cells) hree days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions (p38 inhibitor PD169316).

Project description:Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in presence of Leukaemia Inhibitory Factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38a MAP kinase activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD 169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at three days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene which prevents apoptosis of early differentiated cells.

2007-11-23 | E-GEOD-2042 | biostudies-arrayexpress

Transcriptome of ESCs, EpiSCs and reverted ES by MM401 (Mll1 inhibitor) #2

Project description:This study describes the transcriptome profiling of: 1) mouse ES cells in LIF/KSR medium; 2)EpiSCs in bFGF/serum-free (KSR) medium; 3) EpiSCs treated with MM401/LIF KSR at D3 and D6 (P2); 4) rES reverted form EpiSC by MM401/LIF KSR treatment at P6, P30 with or without MM401 .

2016-05-21 | GSE73993 | GEO

Transcription profiling by array of mouse wild type and E-cadherin knockout embryonic stem cells grown with or without cytokine leukemia inhibitory factor

Project description:We previously observed that E-cadherin knockout embryonic stem cells do not differentiate in the absence of the cytokine leukemia inhibitory factor (LIF) (Soncin et al., 2009, Stem Cells 27 p2069-2080). This experiment was designed to compare the transcription profile of E-cadherin KO ES cells cultured in the presence and absence of LIF. We also compared E-cadherin KO ES cells with wild type D3 ES cells grown in the presence of LIF.

2011-06-19 | E-MEXP-2836 | biostudies-arrayexpress

Pluripotency-state-dependent Role of Dax1 in Embryonic Stem Cells Self-renewal

Project description:DAX1 (also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. We reported that 2i/LIF-ESCs had significantly lower Dax1 expression than LIF/serum-ESCs. Dax1KO ES cell lines could be established in 2i/LIF and their pluripotency was confirmed. In contrast, Dax1-null ESCs could not be continuously passaged in LIF/serum due to severe differentiation and apoptosis. In LIF/serum, the activities of the Core module and Myc module were significantly reduced, while the PRC2 module was activated after Dax1KO. The expression of most pro-apoptotic genes and lineage-commitment genes were drastically increased, while the down-regulated expression of anti-apoptotic genes and many pluripotency genes was observed. Our research on the pluripotent state-dependent role of Dax1 provides clues to understand the molecular regulation mechanism at different stages of early embryonic development.

2021-07-21 | GSE168423 | GEO

Transcription profile of FBL-knock down ES cells

Project description:Pluripotent stem cells have been shown to have unique nuclear properties, e.g., hyperdynamic chromatin and large, condensed nucleoli. However, the contribution of the latter unique nucleolar character to pluripotency has not been well understood. Here, we show fibrillarin (FBL), a critical methyltransferase for ribosomal RNA (rRNA) processing in nucleoli, as one of the proteins highly expressed in pluripotent embryonic stem (ES) cells. Stable expression of FBL in ES cells prolonged the pluripotent state of mouse ES cells cultured in the absence of leukemia inhibitory factor (LIF). Analyses using deletion mutants and a point mutant revealed that the methyltransferase activity of FBL regulates stem cell pluripotency. Knock down of this gene led to significant delays in rRNA processing, growth inhibition, and apoptosis in mouse ES cells. Interestingly, both partial knock down of FBL and treatment with actinomycin D, an inhibitor for rRNA synthesis, induced the expression of differentiation markers in the presence of LIF and promoted stem cell differentiation into neuronal lineages. Moreover, we identified p53 signaling as the regulatory pathway for pluripotency and differentiation of ES cells. These results suggest that proper activity of rRNA production in nucleoli is a novel factor for the regulation of pluripotency and differentiation ability of ES cells. Tc-inducible FBL-knock down ES cells were cultured for 2 days with or without Tc in the presence of LIF. These 2 conditions were analysed transcription profile.

2014-08-01 | E-GEOD-51139 | biostudies-arrayexpress

Differential gene expression during embryoid body (EB) formation of mouse embryonic stem cells when Hnrnpll was depleted

Project description:This work indicates Hnrnpll depletion mES cells cannot exit from pluripotency programme, showing embryoid body formation deficiency and no spontaneous differentiation withdraw LIF. Hnrnpll promotes multiple ES cell preferred-exon skipping during ES cells differentiation, to reduce the ES cells specific isoform and facilitate ES cells exit from pluripotency towards differentiation.

2020-12-06 | GSE136955 | GEO

Transcription profile of FBL-knock down ES cells

2014-08-01 | GSE51139 | GEO

WT vs Klf5 KO ES

Project description:Homozygous disruption of Bteb2/Klf5, a homolog of Drosophila gap gene Krüppel, led to increased expression of various differentiation marker genes, such as Fgf5, Cdx2, and Brachyury in mouse ES cells without compromising their ability to differentiate into all three germ layers. Upon removal of LIF, Klf5-deficient ES cells showed faster differentiation kinetics than wild-type ES cells. In contrast, overexpression of Klf5 in ES cells suppressed the transcription of differentiation marker genes, and maintained pluripotency in the absence of LIF. In order to search downstream genes of Klf5, we surveyed genes implicated in ES cell proliferation by microarray analysis Keywords: cell type comparison

2008-12-31 | GSE9244 | GEO

RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells (miRNA-Seq)

Project description:We performed an integrated analysis of RNA and proteins at the transition between naÃ¯ve ES cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators were specifically released from translational inhibition mediated by RNA-Induced Silencing Complex (RISC). This suggests that, prior to differentiation, the propensity of ES cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators was reinstated following acute inactivation of RISC, and it correlated with loss of stemness markers and activation of early cell differentiation markers in treated ES cells. We evaluated global miRNA profiles of embryonic stem cells cultured in either 10%FCS+LIF or 2i+LIF and of Epiblast-Like Aggregates derived from ES cells in 10%FCS+LIF or 2iL+LIF.

2016-03-29 | E-GEOD-79654 | biostudies-arrayexpress

Cooperative treatment effectiveness of VE821 and AUY922 in Ewing’s sarcoma cells

Project description:Ewing's sarcoma (ES) is the second most frequent bone cancer during childhood and adolescence originating from a translocation between the EWSR1 and the FLI1 gene, which inactivates BRCA-mediated DNA damage response. Both ATR and HSP90 inhibitors are promising new candidates in the field of ES treatment. We show that the HSP90 inhibitor AUY922 alone induced DNA damages, apoptosis and ER stress, while reducing the abundance of DNA repair proteins. The combinations of the ATR inhibitor VE821 and AUY922 (AUY-VE) led to strong apoptosis induction in ES cell lines, originating from a common set of molecular targets and independent of their p53 status, yet based on different molecular mechanisms. P53 wild-type ES cells activated pro-apoptotic gene transcription and underwent mitochondria-mediated apoptosis. P53 null ES cells, however, accumulated higher level of DNA damage, ER stress and autophagy, finally leading to apoptosis. Moreover, AUY-VE treatment compromised ES cell vitality due to impaired PI3K/AKT/mTOR signaling. Unexpectedly, the combinations of AUY922 with the ATM inhibitor, KU55933 failed to kill ES cells and showed protective effects compared to AUY-VE. In summary, we provide mechanistic insights into the effective ES cell killing by ATR and HSP90 inhibitor combinations, which also offers a targetable approach for BRCA-deficient tumors, irrespective of their p53 status and may give rise to new therapeutic strategies.

2021-09-09 | PXD021562 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data