Multimodal single-cell analysis uncovers transcription factor networks underlying T-cell aging
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Aging of the immune system is associated with chronic inflammation and impaired immune function, yet the regulatory mechanisms underlying these changes remain incompletely understood. Here, we generated paired single-cell transcriptomic and chromatin accessibility profiles from peripheral blood mononuclear cells of young and old healthy donors to characterize immune aging at single-cell resolution. Using an integrative computational framework for multi-omic single-cell analysis, we detected pronounced age-associated changes in T cells, including loss of naïve CD8+ T cells and expansion of differentiated memory and effector populations. Aging was accompanied by increased inflammatory signaling and reduced oxidative phosphorylation programs. Enhancer-based gene regulatory network analyses identified a reduced role of TCF7 and increased activity of inflammatory regulators, including FOSL2, in aged T cells. Integration with genetic association and eQTL datasets further supported the functional relevance of age-associated regulatory regions and their target genes.
Authors 9
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
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RWTH Aachen University · Universitätsklinikum Aachen
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Medical Faculty, Aachen, Germany
Institute of Stem Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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RWTH Aachen University · Universitätsklinikum Aachen
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Medical Faculty, Aachen, Germany
Institute of Stem Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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RWTH Aachen University · Universitätsklinikum Aachen
Affiliation as printed
Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Medical Faculty, Aachen, Germany
Institute of Stem Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany
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Hasso Plattner Institute · University of Potsdam · Max Planck Institute for Molecular Genetics
Affiliation as printed
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany
Digital Engineering Faculty, Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany
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RWTH Aachen University · Universitätsklinikum Aachen
Affiliation as printed
Institute for Transfusion Medicine and Cell Therapy, University Hospital of RWTH Aachen, Aachen, Germany
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Freie Universität Berlin · Max Planck Institute for Molecular Genetics
Affiliation as printed
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany
Max Planck Institute for Molecular Genetics, Berlin, Germany
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Hasso Plattner Institute · University of Potsdam · Max Planck Institute for Molecular Genetics
Affiliation as printed
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany
Digital Engineering Faculty, Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany
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Affiliation as printed
Center for Computational Life Sciences, RWTH Aachen University, Aachen, Germany
Institute for Computational Genomics, RWTH Aachen University, Medical Faculty, Aachen, Germany
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