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Transcriptional responses of the human dorsal striatum in opioid use disorder implicates cell type-specifc programs

ABSTRACT: Transcriptional responses of the human dorsal striatum in opioid use disorder implicates cell type-specifc programs

PROVIDER: PRJNA934272 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23438436_1.fastq.gz	Fastqsanger.gz
	SRR23438436_2.fastq.gz	Fastqsanger.gz
	SRR23438437_1.fastq.gz	Fastqsanger.gz
	SRR23438437_2.fastq.gz	Fastqsanger.gz
	SRR23438438_1.fastq.gz	Fastqsanger.gz

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Transcriptional responses of the human dorsal striatum in opioid use disorder implicates cell type-specifc programs

Project description:Gene expression profile at single cell level of striatal cells from the caudate nucleus and putamen in postmortem human brains of unaffected individuals or those with opioid use disorder.

2023-11-28 | GSE225158 | GEO

Single nuclei transcriptomics of human and monkey striatum implicates DNA damage, neuroinflammation, and neurodegeneration signaling in opioid use disorder

Project description:The striatum in the brain is involved in various behavioral functions, including reward, and disease processes, such as opioid use disorder (OUD). Further understanding of the role of striatal subregions in reward behaviors and their potential associations with OUD requires molecular identification of specific striatal cell types in human brain. The human striatum contains subregions based on different anatomical, functional, and physiological properties, with the dorsal striatum further divided into caudate and putamen. Both caudate and putamen are associated with alterations in reward processing, formation of habits, and development of negative affect states in OUD. Using single nuclei RNA-sequencing of human postmortem caudate and putamen, we identified canonical neuronal cell types in striatum (e.g., dopamine receptor 1 or 2 expressing neurons, D1 or D2) and less abundant subpopulations, including D1/D2 hybrid neurons and multiple classes of interneurons. By comparing unaffected subjects to subjects with OUD, we found neuronal-specific differences in pathways related to neurodegeneration, interferon response, and DNA damage. DNA damage markers were also elevated in striatal neurons of rhesus macaques following chronic opioid administration. We identified sex-dependent differences in the expression of stress-induced transcripts (e.g., FKBP5) among astrocytes and oligodendrocytes from female subjects with OUD. Thus, we describe striatal cell types and leverage these data to gain insights into molecular alterations in human striatum associated with opioid addiction.

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Single nuclei transcriptomics of human and monkey striatum implicates DNA damage, neuroinflammation, and neurodegeneration signaling in opioid use disorder

Project description:Single nuclei transcriptomics of human and monkey striatum implicates DNA damage, neuroinflammation, and neurodegeneration signaling in opioid use disorder

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Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum.

Project description:The striatum is the interface between dopamine reward signals and cortico-basal ganglia circuits that mediate diverse behavioral functions. Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and are traditionally classified as direct- or indirect-pathway neurons. However, that traditional model does not explain the anatomical and functional diversity of MSNs. Here, we defined molecularly distinct MSN types in the primate striatum, including (1) dorsal striatum MSN types associated with striosome and matrix compartments, (2) ventral striatum types associated with the nucleus accumbens shell and olfactory tubercle, and (3) an MSN-like type restricted to mu-opioid receptor rich islands in the ventral striatum. These results lay the foundation for achieving cell type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific processing.

2021-11-01 | GSE167920 | GEO

Profiling Neuronal Methylome and Hydroxymethylome of Opioid Use Disorder in the Human Orbitofrontal Cortex

Project description:Opioid use disorder (OUD) is influenced by genetic and environmental factors. While recent research suggests epigenetic disturbances in OUD, this is mostly limited to DNA methylation (5mC). DNA hydroxymethylation (5hmC) has been widely understudied. We conducted a multi-omics profiling of OUD in a male cohort, integrating neuronal-specific 5mC and 5hmC as well as gene expression profiles from human postmortem orbitofrontal cortex (OUD=12; non-OUD=26). Single locus methylomic analysis and co-methylation analysis showed a higher number of OUD-associated genes and gene networks for 5hmC compared to 5mC; these were enriched for GPCR, Wnt, neurogenesis, and opioid signaling. 5hmC marks also showed a higher correlation with gene expression patterns and enriched for GWAS of psychiatric traits. Drug interaction analysis revealed interactions with opioid-related drugs, some used as OUD treatments. Our multi-omics findings suggest an important role of 5hmC and reveal loci epigenetically dysregulated in OFC neurons of individuals with OUD.

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Project description:To uncover the role of opioid induced dysbiosis in disrupting intestinal homeostasis, we conducted a multi-omics analysis with gut microbial, metabolite and intestinal transcriptomics data

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miRNA expression profiles in the dorsal striatum of a mouse model of nicotine withdrawal

Project description:Nicotine withdrawal can diversely affect brain gene expression patterns. In the brain, the dorsal striatum is a hub of nicotine dependence. Previous studies have shown that nicotine dependence leads to functional alterations in the dorsal striatum. miRNAs are small non-coding RNAs that regulates cellular functions and dysfunctions. Here, we performed small RNA sequencing from the dorsal striatum of mice at 7 days after nicotine withdrawal. Our results show that nicotine withdrawal does not notably impact miRNA expression profile in the dorsal striatum, but a few miRNAs were significantly altered in response to nicotine withdrawal. These results suggest that nicotine withdrawal has a small but significant impact on the miRNA expression profile in the mouse dorsal striatum.

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Multi-omics analysis revealing the interplay between gut microbiome and the host following opioid use [ABX-RNA seq]

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Transcriptome profiling of the human dorsal striatum in bipolar disorder

Project description:Bipolar disorder (BD) is a highly heritable and heterogeneous mental illness whose manifestations often include impulsive and risk-taking behavior. This particular phenotype suggests that abnormal striatal function could be involved in BD etiology, yet most transcriptomic studies of this disorder have concentrated on cortical brain regions. We report the first transcriptome profiling by RNA-Seq of the human dorsal striatum comparing bipolar and control subjects. Differential expression analysis and functional pathway enrichment analysis were performed to identify changes in gene expression that correlate with BD status. Further co-expression and enrichment analyses were performed to identify sets of correlated genes that show association to BD. Total RNA samples were isolated from 36 postmortem dorsal striatum subjects (18 bipolar and 18 control) and sequenced. One outlier sample was removed and 35 samples (18 bipolar and 17 control) were analyzed.

2016-08-10 | E-GEOD-80336 | biostudies-arrayexpress

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