Distinct Deregulation Trends of Transcriptional Protein Complexes in Aging Naive T Cells

dc.authoridKokrek, Emel/0000-0002-8379-9617
dc.authorscopusid57211238608
dc.authorscopusid6505565183
dc.authorwosidPir, Pinar/AAA-5103-2022
dc.contributor.authorKökrek, E.
dc.contributor.authorKökrek, Emel
dc.contributor.authorPir, P.
dc.date.accessioned2024-12-15T16:32:59Z
dc.date.available2024-12-15T16:32:59Z
dc.date.issued2025
dc.departmentKadir Has Universityen_US
dc.department-temp[Kökrek E.] Department of Molecular Biology and Genetics, Kadir Has University, Cibali, Kadir Has Cd., Fatih, Istanbul, 34083, Turkey, Department of Bioengineering, Gebze Technical University, Cumhuriyet, 2254. Sk. No:2, Gebze, Kocaeli, 41400, Turkey; [Pir P.] Department of Bioengineering, Gebze Technical University, Cumhuriyet, 2254. Sk. No:2, Gebze, Kocaeli, 41400, Turkeyen_US
dc.description.abstractThe impact of aging on T cell subsets, specifically CD4+ and CD8+ T cells, leading to immune system dysfunction has been the focus of scientific investigation due to its potential to reverse age-associated deterioration. Transcriptomic and epigenomic studies have identified the primary regulators in T cell aging. However, comprehending the underlying dynamic mechanisms requires studying these proteins with their interactors. Here, we integrated single-cell RNA sequencing data of naive CD4+ and CD8+ T cells obtained from 3 different age groups with protein-protein and domain-domain interaction networks to predict and compare the transcriptional protein complexes and identify their capacity to explain age-associated variances. Our novel approach revealed significant effects of aging on the repertoire of complexes, which remains unchanged in naive CD4+ T cells, while in naive CD8+ T cells, it diminishes. In both cell types, there was major deregulation of complexes with the same composition, involving a range of transcription factors. This aging-associated deregulation is characterized by a specific set of protein complexes in naive CD4+ T cells, but this pattern is not observed in naive CD8+ T cells. SMAD3 and BCL11A complexes emerge as key markers in defining a trajectory in aging naive CD4+ T cells. These complexes can accurately distinguish between 3 different age groups, indicating their potential as targets. The direct link between SMAD3 and FOS complexes whose regulatory role has been previously implicated in aging and MBD3 as the novel key link between SMAD3 and BCL11A complexes implicates a coordinated mechanism in age-associated deregulation. © The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.en_US
dc.description.sponsorshipCouncil of Higher Education of Turkey for the Council of Higher Education 100; 2000 Bioinformatics and Biostatistics; Council of Higher Education 100en_US
dc.description.woscitationindexScience Citation Index Expanded
dc.identifier.citationcount0
dc.identifier.doi10.1093/jleuko/qiae231
dc.identifier.issn0741-5400
dc.identifier.issue3en_US
dc.identifier.pmid39437255
dc.identifier.scopus2-s2.0-105001530801
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1093/jleuko/qiae231
dc.identifier.volume117en_US
dc.identifier.wosWOS:001350530300001
dc.identifier.wosqualityQ2
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.relation.ispartofJournal of Leukocyte Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAgingen_US
dc.subjectNaive Cd4+ T Cellen_US
dc.subjectNaive Cd8+ T Cellsen_US
dc.subjectNetwork Analysisen_US
dc.subjectProtein Complexen_US
dc.titleDistinct Deregulation Trends of Transcriptional Protein Complexes in Aging Naive T Cellsen_US
dc.typeArticleen_US
dc.wos.citedbyCount0
dspace.entity.typePublication
relation.isAuthorOfPublicationa3ed1ae3-daa3-4cf1-b36c-e5265d809a3e
relation.isAuthorOfPublication.latestForDiscoverya3ed1ae3-daa3-4cf1-b36c-e5265d809a3e

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