Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RNA-seq data set)

ABSTRACT: Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RNA-seq data set)

PROVIDER: PRJNA434588 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6748810_1.fastq.gz	Fastqsanger.gz
	SRR6748810_2.fastq.gz	Fastqsanger.gz
	SRR6748820_1.fastq.gz	Fastqsanger.gz
	SRR6748820_2.fastq.gz	Fastqsanger.gz
	SRR6748811_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 38

Similar Datasets

Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RRBS-seq data set)

Project description:Human embryonic stem cells (hESCs) can be captured in either a primed state resembling the post-implantation epiblast or in a naïve state resembling the pre-implantation epiblast. Naïve culture conditions allow study of pre-implantation development ex vivo but reportedly lead to chromosomal abnormalities, compromising their utility in research and potential therapeutic applications. Although MEK inhibition is essential for the naïve state, here we show that reduced MEK inhibition facilitates the establishment and maintenance of naïve hESCs that retain naïve-specific transcriptional and DNA methylation patterns yet accrue fewer chromosomal abnormalities. We further show that hESCs cultured under these modified conditions are less prone to apoptosis and proliferate more rapidly. Our results point to the importance of residual MAPK signaling and provide a simple modification to current protocols to enable robust growth and genomic stability in naïve hESCs.

2018-07-10 | GSE111018 | GEO

Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RNA-seq data set)

2018-07-10 | GSE110805 | GEO

Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RRBS-seq data set)

Project description:Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RRBS-seq data set)

| PRJNA435603 | ENA

Reduced MEK inhibition preserves genomic stability in naïve human ES cells

Project description:Reduced MEK inhibition preserves genomic stability in naïve human ES cells

| PRJNA435590 | ENA

Reduced mTORC1 activity is associated with responsiveness to MEK inhibition (PD0325901) in gastric cancer cells.

Project description:Since gastric cancer (GC) is characterized by amplifications of receptor tyrosine kinases (RTK) and KRAS, targeting the RTK/KRAS downstream pathways could contribute to broader applicability of molecular targeted therapy in GC. Here, we assembled a panel of 49 GC cell lines and screened predictors for responsiveness to RAF/MEK/ERK pathway inhibition by comparing their sensitivity to MEK inhibition with alteration status of RTK/KRAS and phosphorylation status of RTK/KRAS downstream molecules. We found that GC cells with MET amplification or KRAS mutation tend to be sensitive to MEK inhibition. Furthermore, lower phosphorylation levels of mTORC1 targets, p70S6K and 4EBP1, was also significantly associated with sensitivity to MEK inhibition. Interestingly, the sensitive cells showed reduced mTORC1 activity accompanied by decreased rate of protein synthesis after MEK inhibition, suggesting that antiproliferative effect of MEK inhibition may be exerted through inhibition of protein synthesis, which was caused by reduced mTORC1 activity. Mechanistically, expression of some mTORC1 negative regulators, such as DDIT4, FOXO3, SESN1 and TSC1, were induced by MEK inhibition in highly-sensitive cell lines and knockdown of these negative regulators partially alleviated the suppression of mTORC1 activity and antiproliferative effect of MEK inhibition. Our data suggest that a subset of GCs, which would be distinguishable according to the predictive markers we identified, may be sensitive to MEK inhibition and have implications for the strategy in clinical trial of MEK inhibitors for GC.

2016-12-31 | GSE74842 | GEO

Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity [RNA-seq]

Project description:Disruption of the MAPK pathway in cancer by kinase inhibition often fails due to pathway reactivation, causing clinical relapse. Among MAPK inhibitors, type I RAF inhibitors are only active against specific BRAF mutants; MEK inhibitor monotherapy is associated with limited clinical benefits but may serve as a foundation for combinatorial therapy. Here, we show that type II RAF plus allosteric MEK inhibitors durably blunt the development of acquired MEK inhibitor resistance among cancers with KRAS, NRAS, NF1, BRAFnon-V600 and BRAFV600 mutations, when compared to a combination of type II RAF plus ERK inhibitors. Type II RAF and MEK (versus ERK) inhibitors also display superior capacity to sequester MEK in RAF complexes and uncouple MEK and ERK interaction in acquired resistant tumor subpopulations. Systemically and intratumorally, type II RAF plus MEK inhibitors expand memory and activated/exhausted CD8+ T-cells. Whereas trametinib alone temporally reduces dominant intra-tumoral T-cell clones, type II RAF inhibitor co-treatment reverses this effect and promotes T-cell clonotypic expansion and convergence. Importantly, durably control of tumors by this combination requires CD8+ T-cells. Thus, the prolonged anti-tumor efficacy of type II RAF plus MEK inhibitors reveals exquisite MAPK addiction in common lethal cancer histologies, and the mechanisms include unexpected allosteric perturbation of the MAPK pathway and engagement of anti-tumor CD8+ T-cell immunity.

2021-06-06 | GSE158607 | GEO

Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity [TCR-seq]

2021-06-06 | GSE158608 | GEO

Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Anti-Tumor T-cell Immunity [single-cell RNA-seq]

2021-06-06 | GSE158609 | GEO

Human ES cells reveal recurrent genomic instability at 20q11.21

Project description:By analyzing five human embryonic stem (hES) cell lines over long-term culture, we detected a recurrent genomic instability in the human genome. An amplification of 2.5–4.6 Mb at 20q11.21, encompassing about 23 genes in common, appeared in four cell lines of different origins. This amplification, which has been associated with oncogenic transformation, may provide a selective advantage to hES cells in culture

2008-11-19 | GSE13565 | GEO

Reduced MEK inhibition preserves genomic stability in naïve human ES cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-07-10 | GSE111020 | GEO