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Transcriptome analysis is one promising approach for characterizing PD and other neurodegenerative disorders by informing how specific disease events influence gene expression and contribute to pathogenesis. With the emergence of single-cell and single-nucleus RNA sequencing (scnRNA-seq) technologies, the transcriptional landscape of neurodegenerative diseases can now be described at the cellular level. As the application of scnRNA-seq is\u00a0becoming routine, it calls to question how results at a single-cell resolution compare to those obtained from RNA sequencing of whole tissues (bulk RNA-seq), whether the findings are compatible, and how the assays are complimentary for unraveling the elusive transcriptional changes that drive neurodegenerative disease. Herein, we review the studies that have leveraged RNA-seq technologies to investigate PD. Through the integration of bulk and scnRNA-seq findings from human, post-mortem brain tissue, we use the PD literature as a case study to evaluate the compatibility of the results generated from each assay and demonstrate the complementarity of the sequencing technologies. Finally, through the lens of the PD transcriptomic literature, we evaluate the current feasibility of bulk and scnRNA-seq technologies to illustrate the necessity of both technologies for achieving a comprehensive insight into the mechanism by which gene expression promotes neurodegenerative disease. We conclude that the continued application of both assays will provide the greatest insight into neurodegenerative disease pathology, providing both cell-specific and whole-tissue level information.<\/jats:p>","DOI":"10.1007\/s12035-024-04124-5","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T11:02:00Z","timestamp":1712314920000},"page":"8996-9015","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Transcriptomics of Human Brain Tissue in Parkinson\u2019s Disease: a Comparison of Bulk and Single-cell RNA Sequencing"],"prefix":"10.1007","volume":"61","author":[{"given":"Michael R.","family":"Fiorini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison A.","family":"Dilliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhalena A.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5936-0957","authenticated-orcid":false,"given":"Sali M. 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