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.
More...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.
Overall design: Refer to individual Series
Less...Accession | PRJNA975616; GEO: GSE233279 |
Type | Umbrella project |
Publications | Phan BN et al., "Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.", Nat Commun, 2024 Jan 31;15(1):878 |
Grants | - "Interpreting the regulatory mechanisms underlying the predisposition to substance use disorders" (Grant ID DP1 DA046585, National Institute on Drug Abuse)
- "Integrating primate-rodent cell types and epigenomics to identify conservation in substance addiction" (Grant ID F30 DA053020, National Institute on Drug Abuse)
- "Delineating the role of serotonin 5-HT2 receptors in opioid use disorders:Development of novel 5-HT2 modulators with translational studies in rodents andprimates" (Grant ID R01 DA047130, National Institute on Drug Abuse)
- "Molecular rhythm alterations in human post-mortem brain associated with opioid use disorder" (Grant ID R01 DA051390, National Institute on Drug Abuse)
- "Molecular rhythm alterations in human post-mortem brain associated with opioid use disorder" (Grant ID R01 DA051390, National Institute on Drug Abuse)
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Submission | Registration date: 23-May-2023 Pfenning Lab, Computational Biology, Carnegie Mellon University |
Relevance | Superseries |
Project Data:
Resource Name | Number of Links |
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Sequence data |
SRA Experiments | 40 |
Publications |
PubMed | 1 |
PMC | 1 |
Other datasets |
BioSample | 40 |
GEO DataSets | 3 |
Single nuclei transcriptomics of human and monkey striatum implicates DNA damage, neuroinflammation, and neurodegeneration signaling in opioid use disorder encompasses the following 2 sub-projects:
Project Type | Number of Projects |
Transcriptome or Gene expression | 2 |
BioProject accession | Organism | Title |
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PRJNA934272 | Homo sapiens | Transcriptional responses of the human dorsal striatum in opioid use disorder implicates cell type-specifc programs (Pfenning Lab, Computational...) | PRJNA975617 | Macaca mulatta | Single nucleus RNA-seq of the rhesus macaque nucleus accumbens after chronic morphine exposure (Pfenning Lab, Computational...) |
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