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We performed sn-RNA-seq and image-based spatial transcriptomics of human caudate nucleus and putamen (dorsal striatum) from PD and control brain donors to elucidate the diversity of oligodendroglia and how they are affected by the disease. We profiled a total of\u2009~\u2009200.000 oligodendroglial nuclei, defining 15 subclasses, from precursor to mature cells, 4 of which are disease-associated. These PD-specific populations are characterized by the overexpression of heat shock proteins, as well as distinct expression signatures related to immune responses, myelination alterations, and disrupted cell signaling pathways. We have also identified impairments in cell communication and oligodendrocyte development, evidenced by changes in neurotransmitter receptors expression and cell adhesion molecules. In addition, we observed significant disruptions in oligodendrocyte development, with aberrant differentiation trajectories and shifts in cell proportions, particularly in the transition from mature oligodendrocytes to disease-associated states. Quantitative immunohistochemical analysis revealed decreased myelin levels in the PD striatum, which correlated with transcriptomic alterations. Furthermore, spatial transcriptomics mapping revealed the distinct localization of disease-associated populations within the striatum, with evidence of impaired myelin integrity. 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He has a collaborative project with Biogen. Dr. Marco Salas is co-founder of spatialist AB, a spatial omics consulting company.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study does not include living human subjects. Samples were collected from autopsies and have been de-identified. Donors or their next-of-kin provided written informed consent for brain autopsy, and the study was approved by the review board of each brain bank.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"46"}}