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Laboratory of Neural and Vascular Biology, Ministry of Education","award":["NV20230003"],"award-info":[{"award-number":["NV20230003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Parkinson\u2019s disease (PD) involves progressive dopaminergic neuron degeneration and motor deficits. Oligodendrocyte dysfunction contributes to PD pathogenesis through impaired myelination. Methods: Single-nucleus RNA sequencing (snRNA-seq) of PD mice revealed compromised oligodendrocyte differentiation and STAT5B downregulation. Pseudotemporal trajectory analysis via Monocle2 demonstrated impaired oligodendrocyte maturation in PD oligodendrocytes, correlating with reduced myelin-related gene expression (Sox10, Plp1, Mbp, Mog, Mag, Mobp). DoRothEA-predicted regulon activity identified STAT5B as a key transcriptional regulator. Results: Oligodendrocyte-specific STAT5B activation improved myelin integrity, as validated by Luxol Fast Blue staining and transmission electron microscopy; attenuated dopaminergic neuron loss; and improved motor function. Mechanistically, STAT5B binds the MBP promoter to drive transcription, a finding confirmed by the luciferase assay, while the DNMT3A-mediated hypermethylation of the STAT5B promoter epigenetically silences its expression, as verified by MethylTarget sequencing and methylation-specific PCR. Conclusions: DNMT3A inhibited the expression of STAT5B by affecting its methylation, which reduced the transcription of MBP, caused oligodendrocyte myelin damage, and eventually led to dopamine neuron damage and motor dysfunction in an MPTP-induced mouse model. This DNMT3A-STAT5B-MBP axis underlies PD-associated myelin damage, connecting epigenetic dysregulation with oligodendrocyte dysfunction and subsequent PD pathogenesis.<\/jats:p>","DOI":"10.3390\/cells14151145","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:35:11Z","timestamp":1753436111000},"page":"1145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Oligodendrocyte-Specific STAT5B Overexpression Ameliorates Myelin Impairment in Experimental Models of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Yibo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowen","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitong","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-1250","authenticated-orcid":false,"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"Neuroscience Research Center, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"Neuroscience Research Center, Hebei Medical University, Shijiazhuang 050017, China"},{"name":"Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","article-title":"Parkinson\u2019s disease","volume":"397","author":"Bloem","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2008.05570.x","article-title":"The life, death, and replacement of oligodendrocytes in the adult CNS","volume":"107","author":"McTigue","year":"2008","journal-title":"J. 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