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Characterization of a drug-resilient cancer cell phenotype [ATAC-Seq]

ABSTRACT: Characterization of a drug-resilient cancer cell phenotype [ATAC-Seq]

PROVIDER: PRJNA986460 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24991610_1.fastq.gz	Fastqsanger.gz
	SRR24991610_2.fastq.gz	Fastqsanger.gz
	SRR24991611_1.fastq.gz	Fastqsanger.gz
	SRR24991611_2.fastq.gz	Fastqsanger.gz
	SRR24991612_1.fastq.gz	Fastqsanger.gz

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Characterization of a drug-resilient cancer cell phenotype

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Characterization of a drug-resilient cancer cell phenotype [RNA-Seq 1]

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Characterization of a drug-resilient cancer cell phenotype [RNA-Seq 2]

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Characterization of a drug-resilient cancer cell phenotype [ATAC-Seq]

Project description:Resistance to treatment and post-therapy recurrence due to small populations of resistant cells remain core challenges in cancer therapy. The mechanisms underlying therapy resistance are undefined for many patients. Here, we demonstrate that some cancer cells survive therapeutic stress via a transient state of whole genome doubling. At the onset of the polyploidization program, we identified upregulation of key transcriptional regulators, including the early stress-response protein AP-1 and normoxic stabilization of HIF-2α. Moreover, chromatin accessibility is altered and expression of pRB is ablated, and we identified enrichment of AP-1 motif accessibility along with an upregulation of replication-dependent histone variants. Here we demonstrate that AP-1and HIF-2α regulate a therapy resilient and survivor phenotype in cancer cells. Consistent with this, genetic or pharmacologic targeting of AP-1 and HIF-2α reduced the frequency of surviving cells following treatment with chemotherapy. These results suggest a novel avenue for tackling chemotherapy-induced resistance in cancer.

2024-02-10 | GSE235555 | GEO

Characterization of a drug-resilient cancer cell phenotype [RNA-Seq 1]

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Characterization of a drug-resilient cancer cell phenotype [RNA-Seq 2]

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Characterization of a drug-resilient cancer cell phenotype

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

2024-02-09 | GSE235909 | GEO

Project description:Characterization of a drug-resilient cancer cell phenotype.

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Whole genome deconvolution unveils Alzheimer’s resilient epigenetic signature

Project description:Assay for Transposase Accessible Chromatin by sequencing (ATAC-seq) provides an accurate way to depict the chromatin regulatory state and altered mechanisms guiding gene expression in disease. However bulk sequencing entangles information from different cell types and obscures cellular heterogeneity. Here, we develop and validate Cellformer, a novel deep learning method, that deconvolutes bulk ATAC-seq into cell type-specific expression across the whole genome. Cellformer enhances the bulk ATAC-seq resolution and allows an efficient cell type specific open chromatin profiling on large size cohorts at a low cost. Applied to 191 bulk samples from 3 brain regions, Cellformer identifies cell type-specific gene regulatory mechanisms and putative mediators involved in resilient to Alzheimer’s disease (RAD), an uncommon group of cognitively healthy individuals that harbor a high pathological load of Alzheimer’s disease (AD). Cell type-resolved chromatin profiling unveils cell type specific pathways and nominates potential epigenetic mediators underlying RAD that may illuminate therapeutic opportunities to limit the cognitive impact of this highly prevalent yet incurable disease. Cellformer has been made freely and publicly available to advance analysis of high-throughput bulk ATAC-seq in future investigations.

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Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

Project description:A novel model of drug-resistant epilepsy based on the selection of mice treated with phenytoin (PHT) in the 6 Hz seizure model was developed. It leads to the identification of subpopulations of drug-responder and non-responder mice. Transcriptional characterization of the hippocampi from these 2 sub-populations was performed and compared. No significant difference has been observed between the 2 sample groups.

2020-09-11 | GSE157797 | GEO

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