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Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Alzheimer\u2019s disease (AD) is a common and increasing societal problem due to the extending human lifespan. In males, loss of chromosome Y (LOY) in leukocytes is strongly associated with AD. We studied here DNA methylation and RNA expression in sorted monocytes and granulocytes with and without LOY from male AD patients. Through multi-omic analysis, we identified new candidate genes along with those previously associated with AD. Global analyses of DNA methylation in samples with LOY vs. normal state showed that hypomethylation dominated both in granulocytes and monocytes. Our findings highlight LOY-related differences in DNA methylation that occur in gene regulatory regions. Specifically, we observed alterations in key genes involved in leukocyte differentiation: <jats:italic>FLI1<\/jats:italic>, involved in early hematopoiesis; <jats:italic>RUNX1<\/jats:italic>, essential for blood cell development; <jats:italic>RARA<\/jats:italic>, regulating gene expression in response to retinoic acid; <jats:italic>CANX<\/jats:italic>, crucial for protein folding; <jats:italic>CEBPB<\/jats:italic>, a transcription factor important for immune responses; and <jats:italic>MYADM<\/jats:italic>, implicated in cell adhesion and migration. Moreover, protein\u2013protein interaction analysis in granulocytes identified that products of two of these genes, <jats:italic>CANX<\/jats:italic> and <jats:italic>CEBPB<\/jats:italic>, are key hub proteins. This research underscores the potential of multi-omic approach in pure hematopoietic cell populations to uncover the molecular underpinnings of AD. Finally, our results link previous analysis showing impact of LOY on leukocyte differentiation, LOY-associated transcriptional dysregulation and GWAS studies of LOY.<\/jats:p>","DOI":"10.1007\/s00018-025-05618-8","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T14:38:11Z","timestamp":1740494291000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer\u00b4s disease"],"prefix":"10.1007","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5481-9148","authenticated-orcid":false,"given":"Marcin","family":"J\u0105kalski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2141-0247","authenticated-orcid":false,"given":"Bo\u017cena","family":"Bruhn-Olszewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Rychlicka-Buniowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniil","family":"Sarkisyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Siedlar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Baran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazimierz","family":"W\u0119glarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Jaszczynski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Ry\u015b","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilmantas","family":"Gedraitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Filipowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Klich-R\u0105czka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Kilander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ingelsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1489-1452","authenticated-orcid":false,"given":"Jan P.","family":"Dumanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"5618_CR1","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/ng.2966","volume":"46","author":"LA Forsberg","year":"2014","unstructured":"Forsberg LA, Rasi C, Malmqvist N, Davies H, Pasupulati S, Pakalapati G, Sandgren J, de Stahl TD, Zaghlool A, Giedraitis V, Lannfelt L, Score J, Cross NC, Absher D, Janson ET, Lindgren CM, Morris AP, Ingelsson E, Lind L, Dumanski JP (2014) Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer. 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Kamatani Y, Finucane H, Hoffmann E, Jackson S, Stefansson K, Auton A, Ong K, Machiela M, Loh P-R, Dumanski J, Chanock S, Forsberg L, Perry J: Genetic predisposition to mosaic Y chromosome loss in blood, Nature 575:652\u2013657","journal-title":"Nature"},{"key":"5618_CR3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41588-018-0267-9","volume":"51","author":"L Forsberg","year":"2019","unstructured":"Forsberg L, Halvardson J, Rychlicka E, Danielsson M, Torabi Moghadam B, Mattisson J, Rasi C, Davies H, Lind L, Giedraitis V, Lannfelt L, Kilander L, Ingelsson M, Dumanski J (2019) Mosaic loss of chromosome Y (LOY) in leukocytes matters. 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