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To address the regional and age\u2010related heterogeneity of human mature oligodendrocytes (MOLs) we applied single\u2010cell RNA sequencing to cells isolated from cortical\/subcortical, subventricular zone brain tissue samples, and thoracolumbar spinal cord samples. Unsupervised clustering of cells identified transcriptionally distinct MOL subpopulations across regions. Spinal cord MOLs, but not microglia, exhibited cell\u2010type\u2010specific upregulation of immune\u2010related markers compared to the other adult regions. SVZ MOLs showed an upregulation of select number of development\u2010linked transcription factors compared to other regions; however, pseudotime trajectory analyses did not identify a global developmental difference. Age\u2010related analysis of cortical\/subcortical samples indicated that pediatric MOLs, especially from under age 5, retain higher expression of genes linked to development and to immune activity with pseudotime analysis favoring a distinct developmental stage. Our regional and age\u2010related studies indicate heterogeneity of MOL populations in the human CNS that may reflect developmental and environmental influences.<\/jats:p>","DOI":"10.1002\/glia.24230","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T12:50:38Z","timestamp":1655988638000},"page":"1938-1949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Regional and age\u2010related diversity of human mature oligodendrocytes"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-5930","authenticated-orcid":false,"given":"Moein","family":"Yaqubi","sequence":"first","affiliation":[{"name":"Neuro\u2010immunology Unit, Montreal Neurological Institute and Department of Neurology and Neurosurgery McGill University  Montreal 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