{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:30:30Z","timestamp":1787049030523,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/22\/17104370\/RECAST"],"award-info":[{"award-number":["INTER\/22\/17104370\/RECAST"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/EJP RD22\/17027921\/PreDYT"],"award-info":[{"award-number":["INTER\/EJP RD22\/17027921\/PreDYT"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/JPND23\/17999421\/AD\u2010PLCG2"],"award-info":[{"award-number":["INTER\/JPND23\/17999421\/AD\u2010PLCG2"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/TRANSCAN23\/18333087\/EPI_T\u2010ALL"],"award-info":[{"award-number":["INTER\/TRANSCAN23\/18333087\/EPI_T\u2010ALL"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["FNR\/NCER13\/BM\/11264123"],"award-info":[{"award-number":["FNR\/NCER13\/BM\/11264123"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The mechanisms that predispose dopaminergic neurons (DAN) to degeneration in Parkinson's disease (PD) are incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To perform an integrative multi\u2010omics reanalysis of single\u2010cell transcriptomic and epigenomic data to identify convergent alterations predisposing dopaminergic neurons to degeneration in Parkinson's disease, and to generate new bulk ATAC\u2010seq profiles from peripheral monocytes to assess whether these alterations extend to a systemic, cross\u2010tissue epigenetic signature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reanalyzed single\u2010cell RNA sequencing (scRNA\u2010seq; n\u2009=\u200927 PD, 11 controls) and single\u2010cell ATAC sequencing (scATAC\u2010seq; n\u2009=\u200910 PD, 2 controls) data from induced pluripotent stem cell (iPSC)\u2013derived DANs (Foundational Data Initiative for Parkinson's Disease [FOUNDIN\u2010PD]) to identify convergent transcriptional and epigenetic alterations. We generated new bulk ATAC\u2010seq from peripheral monocytes of parkinsonian disorder patients (n\u2009=\u200910) and controls (n\u2009=\u20094) to assess cross\u2010tissue epigenetic signatures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Convergent downregulation in neurodevelopmental and synaptic pathways was observed across neuronal maturation stages. Network perturbation analysis identified\n                      <jats:italic>SMARCA4<\/jats:italic>\n                      as a key upstream regulator. Monocyte comparison revealed 44 genes with concordant chromatin accessibility changes, with\n                      <jats:italic>NFATC2<\/jats:italic>\n                      exhibiting decreased accessibility across all neuronal subtypes and monocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This exploratory analysis identifies shared transcriptomic\u2013epigenomic alterations at gene, pathway, and network levels in PD neurons and preliminary systemic epigenetic signatures that warrant validation in larger cohorts. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  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Epigenetics Group, Department of Life Science and Medicine (DLSM), University of Luxembourg  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1709-5312","authenticated-orcid":false,"given":"Tony","family":"Heurtaux","sequence":"additional","affiliation":[{"name":"Systems Biology and Epigenetics Group, Department of Life Science and Medicine (DLSM), University of Luxembourg  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7353-2943","authenticated-orcid":false,"given":"Borja","family":"Gomez\u2010Ramos","sequence":"additional","affiliation":[{"name":"Systems Biology and Epigenetics Group, Department of Life Science and Medicine (DLSM), University of Luxembourg  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-3027","authenticated-orcid":false,"given":"Lasse","family":"Sinkkonen","sequence":"additional","affiliation":[{"name":"Systems Biology and Epigenetics Group, Department of Life Science and Medicine (DLSM), University of Luxembourg  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3977-7469","authenticated-orcid":false,"given":"Enrico","family":"Glaab","sequence":"additional","affiliation":[{"name":"Biomedical Data Science Group Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg  6, avenue du Swing Belval L\u20104367 Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the NCER\u2010PD 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