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Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development.
Durek, Pawel; Nordström, Karl; Gasparoni, Gilles; Salhab, Abdulrahman; Kressler, Christopher; de Almeida, Melanie; Bassler, Kevin; Ulas, Thomas; Schmidt, Florian; Xiong, Jieyi; Glazar, Petar; Klironomos, Filippos; Sinha, Anupam; Kinkley, Sarah; Yang, Xinyi; Arrigoni, Laura; Amirabad, Azim Dehghani; Ardakani, Fatemeh Behjati; Feuerbach, Lars; Gorka, Oliver; Ebert, Peter; Müller, Fabian; Li, Na; Frischbutter, Stefan; Schlickeiser, Stephan; Cendon, Carla; Fröhler, Sebastian; Felder, Bärbel; Gasparoni, Nina; Imbusch, Charles D; Hutter, Barbara; Zipprich, Gideon; Tauchmann, Yvonne; Reinke, Simon; Wassilew, Georgi; Hoffmann, Ute; Richter, Andreas S; Sieverling, Lina; Chang, Hyun-Dong; Syrbe, Uta; Kalus, Ulrich; Eils, Jürgen; Brors, Benedikt; Manke, Thomas; Ruland, Jürgen; Lengauer, Thomas; Rajewsky, Nikolaus; Chen, Wei; Dong, Jun; Sawitzki, Birgit.
Afiliação
  • Durek P; Experimental Rheumatology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Nordström K; Department of Genetics, University of Saarland, 66123 Saarbrücken, Germany.
  • Gasparoni G; Department of Genetics, University of Saarland, 66123 Saarbrücken, Germany.
  • Salhab A; Department of Genetics, University of Saarland, 66123 Saarbrücken, Germany.
  • Kressler C; Experimental Rheumatology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • de Almeida M; Experimental Rheumatology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Bassler K; Life and Medical Sciences Institute, Genomics and Immunoregulation, University of Bonn, 53115 Bonn, Germany.
  • Ulas T; Life and Medical Sciences Institute, Genomics and Immunoregulation, University of Bonn, 53115 Bonn, Germany.
  • Schmidt F; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany; Excellence Cluster on Multimodal Computing and Interaction, Saarland University, 66123 Saarbrücken, Germany.
  • Xiong J; Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • Glazar P; Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • Klironomos F; Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • Sinha A; Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.
  • Kinkley S; Otto Warburg Laboratories: Epigenomics at Max Plank Institute for Molecular Genetics, 14195 Berlin, Germany.
  • Yang X; Otto Warburg Laboratories: Epigenomics at Max Plank Institute for Molecular Genetics, 14195 Berlin, Germany.
  • Arrigoni L; Max Planck Institute of Immunobiology and Epigenetics, 78108 Freiburg, Germany.
  • Amirabad AD; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany; Excellence Cluster on Multimodal Computing and Interaction, Saarland University, 66123 Saarbrücken, Germany.
  • Ardakani FB; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany; Excellence Cluster on Multimodal Computing and Interaction, Saarland University, 66123 Saarbrücken, Germany.
  • Feuerbach L; Applied Bioinformatics, Deutsches Krebsforschungszentrum, 59120 Heidelberg, Germany.
  • Gorka O; Institute for Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University 81675 Munich, Germany.
  • Ebert P; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
  • Müller F; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
  • Li N; Otto Warburg Laboratories: Epigenomics at Max Plank Institute for Molecular Genetics, 14195 Berlin, Germany.
  • Frischbutter S; Experimental Rheumatology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Schlickeiser S; Institute of Medical Immunology, Charité University Medicine, 13353 Berlin, Germany.
  • Cendon C; Cell Biology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Fröhler S; Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • Felder B; Data Management and Genomics IT, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
  • Gasparoni N; Department of Genetics, University of Saarland, 66123 Saarbrücken, Germany.
  • Imbusch CD; Applied Bioinformatics, Deutsches Krebsforschungszentrum, 59120 Heidelberg, Germany.
  • Hutter B; Applied Bioinformatics, Deutsches Krebsforschungszentrum, 59120 Heidelberg, Germany.
  • Zipprich G; Data Management and Genomics IT, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
  • Tauchmann Y; Institut für Transfusionsmedizin, Charité University Medicine, 12203 Berlin, Germany.
  • Reinke S; Berlin-Brandenburg Center for Regenerative Therapies, 13353 Berlin, Germany.
  • Wassilew G; Center for Musculoskeletal Surgery, Charité University Medicine, 10117 Berlin, Germany.
  • Hoffmann U; Experimental Rheumatology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Richter AS; Max Planck Institute of Immunobiology and Epigenetics, 78108 Freiburg, Germany.
  • Sieverling L; Applied Bioinformatics, Deutsches Krebsforschungszentrum, 59120 Heidelberg, Germany.
  • Chang HD; Cell Biology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Syrbe U; Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité University Medicine, 12000 Berlin, Germany.
  • Kalus U; Institut für Transfusionsmedizin, Charité University Medicine, 12203 Berlin, Germany.
  • Eils J; Data Management and Genomics IT, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
  • Brors B; Applied Bioinformatics, Deutsches Krebsforschungszentrum, 59120 Heidelberg, Germany.
  • Manke T; Max Planck Institute of Immunobiology and Epigenetics, 78108 Freiburg, Germany.
  • Ruland J; Institute for Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University 81675 Munich, Germany; German Cancer Consortium (DKTK), 59120 Heidelberg, Germany; German Center for Infection Research (DZIF), partner site 81675 Munich, Germany.
  • Lengauer T; Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbrücken, Germany.
  • Rajewsky N; Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • Chen W; Berlin Institute for Medical Systems Biology, Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
  • Dong J; Cell Biology, German Rheumatism Research Centre, 10117 Berlin, Germany.
  • Sawitzki B; Institute of Medical Immunology, Charité University Medicine, 13353 Berlin, Germany.
Immunity ; 45(5): 1148-1161, 2016 11 15.
Article em En | MEDLINE | ID: mdl-27851915
The impact of epigenetics on the differentiation of memory T (Tmem) cells is poorly defined. We generated deep epigenomes comprising genome-wide profiles of DNA methylation, histone modifications, DNA accessibility, and coding and non-coding RNA expression in naive, central-, effector-, and terminally differentiated CD45RA+ CD4+ Tmem cells from blood and CD69+ Tmem cells from bone marrow (BM-Tmem). We observed a progressive and proliferation-associated global loss of DNA methylation in heterochromatic parts of the genome during Tmem cell differentiation. Furthermore, distinct gradually changing signatures in the epigenome and the transcriptome supported a linear model of memory development in circulating T cells, while tissue-resident BM-Tmem branched off with a unique epigenetic profile. Integrative analyses identified candidate master regulators of Tmem cell differentiation, including the transcription factor FOXP1. This study highlights the importance of epigenomic changes for Tmem cell biology and demonstrates the value of epigenetic data for the identification of lineage regulators.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Diferenciação Celular / Epigênese Genética / Epigenômica / Memória Imunológica Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Diferenciação Celular / Epigênese Genética / Epigenômica / Memória Imunológica Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article