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To better understand the cellular changes associated with DS, we investigated the cell composition in blood, brain, and buccal swab samples from DS patients and controls using DNA methylation-based cell-type deconvolution. We used genome-scale DNA methylation data from Illumina HumanMethylation450k and HumanMethylationEPIC arrays to profile cell composition and trace fetal lineage cells in blood samples (DS N = 46; control N = 1469), brain samples from various regions (DS N = 71; control N = 101), and buccal swab samples (DS N = 10; control N = 10). In early development, the number of cells from the fetal lineage in the blood is drastically lower in DS patients (\u0394 = 17.5%), indicating an epigenetically dysregulated maturation process for DS patients. Across sample types, we observed significant alterations in relative cell-type proportions for DS subjects compared with the controls. Cell-type proportion alterations were present in samples from early development and adulthood. Our findings provide insight into DS cellular biology and suggest potential cellular interventional targets for DS.<\/jats:p>","DOI":"10.3390\/cells12081168","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T01:34:15Z","timestamp":1681695255000},"page":"1168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Down Syndrome Altered Cell Composition in Blood, Brain, and Buccal Swab Samples Profiled by DNA-Methylation-Based Cell-Type Deconvolution"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9854-5823","authenticated-orcid":false,"given":"Ze","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah G.","family":"Stolrow","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brock C.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA"},{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2279-4097","authenticated-orcid":false,"given":"Lucas A.","family":"Salas","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA"},{"name":"Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/bdr2.1589","article-title":"National population-based estimates for major birth defects, 2010\u20132014","volume":"111","author":"Mai","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13244-019-0729-3","article-title":"Neuroimaging assessment in Down syndrome: A pictorial review","volume":"10","author":"Rodrigues","year":"2019","journal-title":"Insights Imaging"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. 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