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| Status |
Public on Nov 28, 2023 |
| Title |
Single nuclei transcriptomics of human and monkey striatum implicates DNA damage, neuroinflammation, and neurodegeneration signaling in opioid use disorder |
| Organisms |
Macaca mulatta; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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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| Overall design |
Refer to individual Series
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| Web link |
https://www.nature.com/articles/s41467-024-45165-7
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| Citation(s) |
38296993 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| F30 DA053020 |
Integrating primate-rodent cell types and epigenomics to identify conservation in substance addiction |
CARNEGIE MELLON UNIVERSITY |
Badoi Nguyen Phan |
| R01 DA051390 |
Molecular rhythm alterations in human post-mortem brain associated with opioid use disorder |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
Ryan W Logan |
| R01 DA051390 |
Molecular rhythm alterations in human post-mortem brain associated with opioid use disorder |
UNIVERSITY OF PITTSBURGH AT PITTSBURGH |
Marianne L Seney |
| DP1 DA046585 |
Interpreting the regulatory mechanisms underlying the predisposition to substance use disorders |
CARNEGIE MELLON UNIVERSITY |
Andreas Robert Pfenning |
| R01 DA047130 |
Delineating the role of serotonin 5-HT2 receptors in opioid use disorders:Development of novel 5-HT2 modulators with translational studies in rodents andprimates |
NORTHEASTERN UNIVERSITY |
Stephen John Kohut |
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| |
| Submission date |
May 23, 2023 |
| Last update date |
Feb 14, 2024 |
| Contact name |
BaDoi Nguyen Phan |
| E-mail(s) |
badoi.phan@pitt.edu
|
| Organization name |
Carnegie Mellon University
|
| Department |
Computational Biology
|
| Lab |
Pfenning Lab
|
| Street address |
5000 Forbes Ave
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15213 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL27943 |
Illumina NovaSeq 6000 (Macaca mulatta) |
|
| Samples (40)
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| This SuperSeries is composed of the following SubSeries: |
| GSE225158 |
Transcriptional responses of the human dorsal striatum in opioid use disorder implicates cell type-specifc programs |
| GSE233278 |
Single nucleus RNA-seq of the rhesus macaque nucleus accumbens after chronic morphine exposure |
|
| Relations |
| BioProject |
PRJNA975616 |
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