Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE233279 | GEO | 2023/11/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Diurnal alterations in gene expression across striatal subregions in psychosis

Project description:Background: Psychosis is a defining feature of schizophrenia and highly prevalent in bipolar disorder. Notably, individuals suffering with these illnesses also have major disruptions in sleep and circadian rhythms, and disturbances to sleep and circadian rhythms can precipitate or exacerbate psychotic symptoms. Psychosis is associated with the striatum, though no study to date has directly measured molecular rhythms and determined how they are altered in the striatum of subjects with psychosis. Methods: Here, we perform RNA-sequencing and both differential expression and rhythmicity analyses to investigate diurnal alterations in gene expression in human postmortem striatal subregions (NAc, caudate, and putamen) in subjects with psychosis relative to unaffected comparison subjects. Results: Across regions, we find differential expression of immune-related transcripts and a substantial loss of rhythmicity in core circadian clock genes in subjects with psychosis. In the nucleus accumbens (NAc), mitochondrial-related transcripts have decreased expression in psychosis subjects, but only in those who died at night. Additionally, we find a loss of rhythmicity in small nucleolar RNAs and a gain of rhythmicity in glutamatergic signaling in the NAc of psychosis subjects. Between region comparisons indicate that rhythmicity in the caudate and putamen is far more similar in subjects with psychosis than in matched comparison subjects. Conclusions: Together, these findings reveal differential and rhythmic gene expression differences across the striatum that may contribute to striatal dysfunction and psychosis in psychotic disorders.

2022-08-31 | GSE202537 | GEO

Diurnal rhythms across the human dorsal and ventral striatum

Project description:The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a “time of death” approach to identify diurnal rhythms in RNA transcripts in human cortical regions. Here, we identify molecular rhythms across the three striatal subregions collected from postmortem human brain tissue in subjects without psychiatric or neurological disorders. Core circadian clock genes are rhythmic across all three regions and show strong phase concordance across regions. However, the putamen contains a much larger number of significantly rhythmic transcripts than the other two regions. Moreover, there are many differences in pathways that are rhythmic across regions. Strikingly, the top rhythmic transcripts in NAc (but not the other regions) are predominantly snoRNAs and lncRNAs, suggesting that a completely different mechanism might be used for the regulation of diurnal rhythms in translation and/or RNA processing in the NAc versus the other regions. Further, although the NAc and putamen are generally in phase with regards to timing of expression rhythms, the NAc and caudate, and caudate and putamen, have several clusters of discordant rhythmic transcripts, suggesting a temporal wave of specific cellular processes with the caudate preceding the other regions. Taken together, these studies reveal distinct transcriptome rhythms across the human striatum and are an important step in helping to understand the normal function of diurnal rhythms in these regions and how disruption could lead to pathology.

2020-12-31 | GSE160521 | GEO

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

Comparative rhythmic transcriptome profiling of human and mouse striatal subregions

Project description:The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). In mice, this roughly corresponds to the dorsal medial striatum (DMS), dorsal lateral striatum (DLS), and ventral striatum (NAc). Each of these structures have some overlapping and distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a “time-of-death” approach to identify diurnal rhythms in RNA transcripts in these three human striatal subregions. Here, we identify molecular rhythms across similar striatal subregions collected from C57BL/6J mice across 6 times of day and compare results to the human striatum. Pathway analysis indicates a large degree of overlap between species in rhythmic transcripts involved in processes like cellular stress, energy metabolism, and translation. Notably, a striking finding in humans is that small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) are among the most highly rhythmic transcripts in the NAc and this is not conserved in mice, suggesting the rhythmicity of RNA processing in this region could be uniquely human. Furthermore, the peak timing of overlapping rhythmic genes is altered between species, but not consistently in one direction. Taken together, these studies reveal conserved as well as distinct transcriptome rhythms across the human and mouse striatum and are an important step in understanding the normal function of diurnal rhythms in humans and model organisms in these regions and how disruption could lead to pathology.

2024-02-03 | GSE254949 | GEO

Innovations in primate interneuron repertoire

Project description:We report single-nucleus transcriptomes from brain regions in 5 species: mice: Frontal Cortex, V1, Hippocampus, Striatum; common marmoset: 7 neocortical regions, Hippocampus, Striatum (Nucleus Accumbens, Caudate, Putamen); rhesus macaque: Prefrontal Cortex, V1; human: Prefrontal Cortex, V1, Striatum (Caudate); ferret: Prefrontal Cortex, V1, Striatum

2020-06-04 | GSE151761 | GEO

Sp8 and Sp9 coordinately promote D2-type medium spiny neuron production by activating Six3 expression [ChIP-Seq]

Project description:D1- and D2-type medium spiny neurons (MSNs) are the principal projection neurons in the striatum, including in the dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle) that are generated by the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the Sp8 and Sp9 transcription factors (TFs) selectively have a severe reduction in D2 MSNs due to reduced neurogenesis in the LGE. Sp8/9 together drive expression of the Six3 TF in a spatial restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 loss of function. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3. This study provides evidence for components of a transcription pathway, in a regionally restricted LGE domain, that selectively drives the generation of D2 MSNs.

2018-05-11 | GSE114306 | GEO

Blood RNAs predictive of molecular changes in the brain and clinical outcome in Parkinson’s disease

Project description:The ability to use blood to predict the outcomes of Parkinson’s disease (PD), including disease progression and development of cognitive and motor complications, would be of enormous clinical value. We undertook deep RNA sequencing from the caudate and putamen of postmortem PD (n=35) and control (n=40) striatum, and compared molecular profiles with clinical features, and samples obtained from antemortem peripheral blood from an independent cohort. Cognitive and motor complications of PD were associated with molecular changes in the caudate (e.g., stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset PD were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence) respectively. Molecular signatures in the postmortem PD brain were also evident in antemortem peripheral blood, and correlated with clinical disease features. Together, these findings identify molecular signatures in PD patients' brain and blood of potential pathophysiologic and prognostic importance

2023-07-05 | PXD042154 | Pride

Genome-wide analysis of RARÎ² transcriptional targets in mouse striatum links retinoic acid signaling with Huntingtonâs disease and other neurodegenerative disorders

Project description:The active vitamin A derivative retinoic acid (RA) is an important regulator of adult brain functions. How these regulations are achieved is poorly known, partly due to the paucity of information on RA molecular targets. The striatum, the region involved in control of motor, cognitive and affective functions, may be particularly prone to such regulation as it displays the highest levels of RA and its receptors (RARs). We report the first genome-wide analysis of RAR-binding sites in the brain. Using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq), as well as transcriptomic analysis of RARÎ²-null mutant mice, we identified genomic transcriptional targets of RARÎ² in the striatum. Our data point to a strong contribution of RARÎ² in controlling neurotransmission, energy metabolism, and transcription, with a particular involvement of G-protein, cAMP and calcium signaling. Quantitative PCR analysis of striatal subregions revealed a higher sensitivity of ventral structures (nucleus accumbens) to lack of RARÎ² signaling. There is a high overlap of transcriptional targets of RARÎ² and genes affected in expression in Huntingtonâs disease (HD), and we observed a decrease of RARÎ² expression in the striatum of R6/2 transgenic mice, a murine model of HD. A large number of genes bearing RARÎ² binding sites have also been implicated in Alzheimerâs and Parkinsonâs diseases, raising the possibility that compromised RA signaling in striatum may be a mechanistic link explaining the similar affective and cognitive symptoms of these diseases. Globally, our data point to a possibility of a neuroprotective function of RARÎ² in the striatum. Genome-wide mapping of RARÎ² and H3K4me3 binding sites in mouse caudate putamen

2016-07-22 | E-GEOD-67829 | biostudies-arrayexpress

Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder

Project description:Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC

2021-06-12 | GSE174409 | GEO

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data