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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation

ABSTRACT: Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation

PROVIDER: PRJNA437950 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6826260.fastq.gz	Fastqsanger.gz
	SRR6826270.fastq.gz	Fastqsanger.gz
	SRR6826280.fastq.gz	Fastqsanger.gz
	SRR6826290.fastq.gz	Fastqsanger.gz
	SRR6826310_1.fastq.gz	Fastqsanger.gz

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ATAC-Seq data sets)

Project description:Phenotypic modulation of smooth muscle cells (SMC) is a hallmark of vascular disease and a classic cell state transformation mediated by convergent signal-integration in the nucleus. Here, using PDGF-mediated SMC activation, we describe for the first time the dynamic active chromatin response and global transcriptional remodeling of cell state. We find that PDGF stimulation drives global transcriptional amplification and anabolism concurrent with increased proliferation and motility. Kinetic gene expression and Brd4 chromatin co-activator occupancy analysis reveals transcription factor (TF) directed enhancer re-wiring shaped by an immediate-early (Jun/Fos) response followed by increased nuclear hormone receptor transcriptional signaling that is Rev-erbdependent. Interdicting signaling between enhancers and transcription via Brd4 inhibition halts canonical cellular features of PDGF stimulation, and in vivo Brd4 inhibition potently abrogates vascular injury responses. These data provide a global map of TF-directed chromatin remodeling during SMC phenotypic modulation and elucidate key therapeutic mechanisms of transcriptional inhibition in vascular disease.

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ChIP-Seq data sets)

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ChIP-Rx data sets)

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ATAC-Seq data sets)

Project description:Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ATAC-Seq data sets)

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ChIP-Rx data sets)

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ChIP-Seq data sets)

Project description:Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation (ChIP-Seq data sets)

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Dynamic rewiring of transcription factor networks during smooth muscle cell phenotypic modulation

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

2019-01-01 | GSE111715 | GEO

Single cell analysis of smooth muscle cell phenotypic modulation in vivo during disease in mice and humans [mouse CITE-seq]

Project description:In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human. We performed CITE-seq in mouse atherosclerotic lesions using antibodies directed against several macrophage surface markers. In the mice, we also performed SMC-specific knockout of TCF21, a causal CAD gene, to determine the effect of this gene on SMC phenotypic modulation. Finally, we performed ChIP-seq for the transcription factor TCF21 in a pooled DNA sample comprised of 52 different human coronary artery smooth muscle cell (HCASMC) lines to determine TCF21 target genes.

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