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Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [MACS]

ABSTRACT: Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [MACS]

PROVIDER: PRJNA887744 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21824400_1.fastq.gz	Fastqsanger.gz
	SRR21824400_2.fastq.gz	Fastqsanger.gz
	SRR21824401_1.fastq.gz	Fastqsanger.gz
	SRR21824401_2.fastq.gz	Fastqsanger.gz
	SRR21824402_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [MACS]

Project description:Overall risk for Major Depressive Disorder (MDD) is determined by complex interactions between genetic and environmental factors that influence epigenetic regulation of neuroplasticity and stress pathways1,2. These mechanisms are specific to the distinct regulatory context within regionally-defined brain cell-types3,4. Here, we employed genome-wide chromatin accessibility profiling of neuronal vs. non-neuronal cells in orbitofrontal cortex (OFC) to capture regulatory signatures of MDD. We mapped genetic risk for MDD to active promoters of non-neuronal cell-types in OFC and identified MDD-specific open chromatin regions, which were differentially accessible exclusively in non-neuronal cells. Characterization of these loci revealed a key role for astrocyte dysfunction, and implicated the chromatin remodeling protein ZBTB7A, which coordinates wide-ranging cellular activation programs, including NF-kB inflammatory transcription5. In mice, astrocyte-specific knockdown of Zbtb7a reversed chromatin remodeling, reactive astrocyte transcription, and behavioral deficits associated with chronic stress. Conversely, ZBTB7A overexpression in OFC astrocytes induced stress-related behavioral deficits, promoted widespread inflammatory gene expression, and drove pathophysiological OFC neuronal hyperactivity in response to a mild subthreshold stressor. Our data highlight a critical role for OFC astrocytes in the bidirectional regulation of stress vulnerability and pinpoint ZBTB7A as a key factor mediating maladaptive astrocyte plasticity and OFC neuronal hyperexcitability in MDD.

2023-08-08 | GSE214919 | GEO

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder

Project description:Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder

| PRJNA887741 | ENA

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [MDD]

Project description:Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [MDD]

| PRJNA887745 | ENA

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [MDD]

2023-08-08 | GSE214921 | GEO

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [bulk RNA-Seq]

2023-08-08 | GSE214920 | GEO

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [bulk RNA-Seq]

Project description:Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder [bulk RNA-Seq]

| PRJNA887743 | ENA

Astrocytic ZBTB7A promotes orbitofrontal cortex dysfunction associated with Major Depressive Disorder

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

2023-08-08 | GSE214922 | GEO

To explore the functional consequences of ZBTB7A Overexpression in rodent OFC astrocytes in the context of a mild stressor

Project description:Major Depressive Disorder (MDD) arises from a complex interaction between genetics and environmental influences such as stress, which leads to persistent changes in frontolimbic gene expression and cellular function. Although relatively understudied in depression, the orbitofrontal cortex (OFC) exhibits significant changes in neuronal activity in MDD, as well as widespread gene expression changes, including consistent upregulation of inflammatory stress pathways. Inflammation signaling in non-neuronal cell-types can disrupt normal neurotransmission, though the molecular mechanisms that regulate this interaction are not well understood. Our laboratory has implemented nuclei-sorting coupled with ATAC-seq in human postmortem OFC to characterize over 200 MDD-specific open chromatin regions (OCRs), which were detected exclusively in the non-neuronal cell population. From this dataset, we identified ZBTB7A, a chromatin remodeling protein with binding motifs significantly overrepresented in these MDD-specific OCRs. ZBTB7A has been shown to orchestrate chromatin accessibility for NF-kB target genes, however, its functional role in psychiatric disease has not yet been explored. In a series of studies utilizing astrocyte-specific viral manipulations, we found that overexpressing this chromatin remodeler in rodent OFC astrocytes was sufficient to induce aberrant expression of inflammatory genes, behavioral deficits, and neuronal hyperactivity in response to a mild stressor, compared to GFP-expressing mice. Together, these findings demonstrate a novel chromatin-based mechanism for increased inflammatory signaling in astrocytes that ultimately impairs neuroadaptive responses to stress with direct implications for OFC dysfunction in MDD pathology.

2024-11-07 | GSE174527 | GEO

ZBTB7A ChIP-seq under different DHT level

Project description:Zinc finger and BTB domain containing transcription repressor ZBTB7A has been recently reported as a tumor suppressor who plays important functions to prevent the progression of prostate cancer. However, the chromatin activity of ZBTB7A in prostate cancer cells remain unclear. In order to identify the cistrome and transcriptome of ZBTB7A, we performed ZBTB7A ChIP-seq in VCaP cells and RNA-seq in VCaP cells transfected with siRNA targeting ZBTB7A or non-targeting control, respectively (cells were grown in full serum). By using combined ChIP-seq and RNA-seq analyses in VCaP cells, we have precisely mapped the ZBTB7A binding sites and identified a subset of genes that are directly repressed by ZBTB7A. To study the chromatin interaction of ZBTB7A with androgen receptor (AR), we also performed ChIP-seq of ZBTB7A in VCaP cells stimulated with 10 nM DHT for 4 hours versus vehicle control (cells were hormone-depleted prior to DHT stimulation). Our results show that ZBTB7A binding is increased by androgen at AR and ZBTB7A overlapping sites.

2019-09-12 | GSE123089 | GEO

circular Neurexin3 knockdown in rat orbitofrontal cortex

Project description:We report mRNAs differentially expressed in the orbitofrontal cortex of adult male rats 7 days following knockdown of circular Neurexin 3 in the orbitofrontal cortex.

2024-02-09 | GSE224957 | GEO

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