{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:29:34Z","timestamp":1792099774949,"version":"4.4.0"},"reference-count":57,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"15","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,4,14]]},"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder. However, cell type\u2013dependent transcriptional regulatory programs responsible for PD pathogenesis remain elusive. Here, we establish transcriptomic and epigenomic landscapes of the substantia nigra by profiling 113,207 nuclei obtained from healthy controls and patients with PD. Our multiomics data integration provides cell type annotation of 128,724 cis-regulatory elements (cREs) and uncovers cell type\u2013specific dysregulations in cREs with a strong transcriptional influence on genes implicated in PD. The establishment of high-resolution three-dimensional chromatin contact maps identifies 656 target genes of dysregulated cREs and genetic risk loci, uncovering both potential and known PD risk genes. Notably, these candidate genes exhibit modular gene expression patterns with unique molecular signatures in distinct cell types, highlighting altered molecular mechanisms in dopaminergic neurons and glial cells including oligodendrocytes and microglia. Together, our single-cell transcriptome and epigenome reveal cell type\u2013specific disruption in transcriptional regulations related to PD.<\/jats:p>","DOI":"10.1126\/sciadv.abo2467","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T17:58:17Z","timestamp":1681495097000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":73,"title":["Characterization of altered molecular mechanisms in Parkinson\u2019s disease through cell type\u2013resolved multiomics analyses"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9917-8834","authenticated-orcid":true,"given":"Andrew J.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9936-8195","authenticated-orcid":true,"given":"Changyoun","family":"Kim","sequence":"additional","affiliation":[{"name":"Molecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9612-0020","authenticated-orcid":true,"given":"Seongwan","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5637-6029","authenticated-orcid":true,"given":"Jaegeon","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-9082","authenticated-orcid":true,"given":"Baekgyu","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2311-5794","authenticated-orcid":true,"given":"Dongchan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-5531","authenticated-orcid":true,"given":"Kyoungho","family":"Jun","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5301-6776","authenticated-orcid":true,"given":"Junghyun","family":"Eom","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5155-5335","authenticated-orcid":true,"given":"Seung-Jae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Department of Medicine, Neuroscience Research Institute, Convergence Research Center for Dementia, Seoul National University College of Medicine, Seoul 03080, Republic of Korea."},{"name":"Neuramedy Co. 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