Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder
BaDoi N. Phan, Madelyn H. Ray, Xiangning Xue, Chen Fu, Robert J. Fenster, Stephen J. Kohut, Jack Bergman, Suzanne N. Haber, Kenneth M. McCullough, Madeline K. Fish, Jill R. Glausier, Qiao Su, Allison E. Tipton, David A. Lewis, Zachary Freyberg, George C. Tseng, Shelley J. Russek, Yuriy Alekseyev, Kerry J. Ressler, Marianne L. Seney, Andreas R. Pfenning, Ryan W. Logan
Abstract
In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction is linked to psychiatric disorders, including opioid use disorder (OUD). Striatal subregions are divided based on neuroanatomy, each with unique roles in OUD. In OUD, the dorsal striatum is involved in altered reward processing, formation of habits, and development of negative affect during withdrawal. Using single nuclei RNA-sequencing, we identified both canonical (e.g., dopamine receptor subtype) and less abundant cell populations (e.g., interneurons) in human dorsal striatum. Pathways related to neurodegeneration, interferon response, and DNA damage were significantly enriched in striatal neurons of individuals with OUD. DNA damage markers were also elevated in striatal neurons of opioid-exposed rhesus macaques. Sex-specific molecular differences in glial cell subtypes associated with chronic stress were found in OUD, particularly female individuals. Together, we describe different cell types in human dorsal striatum and identify cell type-specific alterations in OUD.
Datasets
1. Transcriptional responses of the human dorsal striatum in opioid use disorder implicates cell type-specifc programs
Metadata
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scds.keep
miQC.keep
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Dx_OUD
Dx_Substances
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DSM.IV.SUD
DSM.IV.Psych
Blood.Toxicology
Infxn.Dx
Medications.ATODc
Tobacco.ATOD
Manner.of.Death
Cause.of.Death
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Opioid Dependence19550 cells Opioid Dependence; Sedative or Hypnotic or Anxiolytic Dependence14691 cells Opioid Dependence; Alcohol Dependence; Cocaine Dependence; Polysubstance Dependence10504 cells Opioid Dependence; Cocaine Dependence; Sedative or Hypnotic or Anxiolytic Dependence9654 cells Major Depressive Disorder, Single Episode, Severe without Psychotic Features10504 cells Pain Disorder Associated with Both Psychological Factors and a General Medical Condition7941 cells No substances detected44449 cells Methadone, Methadone Metabolite, Trazodone12200 cells Morphine, Phenobarbital, Cocaine Metabolites10504 cells Fentanyl, Norfentanyl, Lidocaine, Butalbital, Cocaine Metabolites, Trazodone, Alprazolam, Citalopram, Acetaminophen9654 cells Methadone, Tramadol, Alprazolam, Diphenhydramine7941 cells Morphine, Oxycodone7350 cells Fentanyl, Meprobamate6750 cells Osteoarthritis; Degenerative Changes of Cervical Spine12200 cells Asthma; Recurrent Bronchitis7941 cells Osteomyelitis with Non-healing Ulcer; Recurring Foot Infections7350 cells Degenerative Joint Disease2883 cells B, C, D, L, O, P6750 cells Combined Drug Overdose47649 cells Endocardial Fibroelastosis14812 cells Pulmonary Embolism14540 cells Cardiovascular Disease9222 cells Fentanyl Overdose6750 cells Cardiac Tamponade3445 cells NCBITaxon:960698848 cells UBERON:000187357571 cells UBERON:000187441277 cells HANCESTRO:000574524 cells HANCESTRO:056824324 cells LR_RM.1034.F.W.2314812 cells LR_RM.1488.M.B.3914540 cells LR_RM.1572.F.W.3512200 cells LR_RM.1252.M.W.4010504 cells LR_RM.1262.M.W.419654 cells LR_RM.1366.F.W.357941 cells LR_RM.1670.M.W.427350 cells LR_RM.13281.F.W.546750 cells LR_RM.13114.F.B.546339 cells LR_RM.13291.M.B.373445 cells LR_RM.13151.F.W.552883 cells LR_RM.612.M.W.602430 cells HsapDv:000012920141 cells HsapDv:000011714812 cells HsapDv:000013314540 cells HsapDv:000014813089 cells HsapDv:000013410504 cells oligodendrocyte62982 cells oligodendrocyte precursor cell6632 cells microglial cell6630 cells indirect pathway medium spiny neuron6172 cells direct pathway medium spiny neuron5385 cells inhibitory interneuron1167 cells medium spiny neuron593 cells endothelial cell581 cells opiate dependence54399 cells caudate nucleus57571 cells African American24324 cells 35-year-old human stage20141 cells 23-year-old human stage14812 cells 39-year-old human stage14540 cells 54-year-old human stage13089 cells 40-year-old human stage10504 cells 41-year-old human stage9654 cells 42-year-old human stage7350 cells 37-year-old human stage3445 cells 55-year-old human stage2883 cells 60-year-old human stage2430 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/cec4ef8e-1e70-49a2-ae43-1e6bf1fd5978
Alias names
GSE233279, PMID38296993, PMC10831093
Cite this study
Phan, B.N., Ray, M.H., Xue, X., Fu, C., Fenster, R.J., Kohut, S.J., Bergman, J., Haber, S.N., McCullough, K.M., Fish, M.K. and Glausier, J.R., 2024. Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder. Nature Communications, 15(1), p.878. https://doi.org/10.1038/s41467-024-45165-7
