Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells
| Autor: | Mourad Hussein, Céline Delaloy, Ana C. Queirós, Elise A. Mahé, Fabrice Chatonnet, José I. Martín-Subero, Maud Lemarié, Gilles Salbert, Marta Kulis, Thierry Fest, Stéphane Avner, Amandine Pignarre, Núria Verdaguer-Dot, Karin Tarte, Gersende Caron |
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| Přispěvatelé: | Universitat de Barcelona, Pôle biologie, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universitat de Barcelona (UB), Etablissement Français du Sang Bretagne, EFS, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was supported by an internal grant from the Hematology laboratory, Pôle de biologie, CHU de Rennes, France, the Ligue Nationale contre le Cancer (Equipe labellisée), and the European Union’s Seventh Framework Program through the Blueprint Consortium. M.H. was supported by a research grant from La Ligue contre le Cancer/Région Bretagne. G.S. was supported by the CNRS and the University of Rennes 1 and by grants from La Ligue contre le Cancer and Cancéropole Grand Ouest. E.A.M. was supported by a Ph.D. fellowship from the Ministère de l’enseignement supérieur et de la recherche. Sequencing was performed by the IGBMC Microarray and Sequencing platform, a member of the France Génomique consortium (ANR-10-INBS-0009), and the Biogenouest Genomics/Human & Environmental Genomics core facility of Rennes (Biosit/OSUR). Cell sorting was performed at the Biosit Flow Cytometry and CellSorting Facility (University of Rennes 1, France)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Jonchère, Laurent, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) |
| Rok vydání: | 2015 |
| Předmět: |
Cèl·lules B
Cellular differentiation Plasma Cells ADN Naive B cell [SDV.CAN]Life Sciences [q-bio]/Cancer plasma cell differentiation Plasma cell Cell fate determination General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine [SDV.CAN] Life Sciences [q-bio]/Cancer Transforming Growth Factor beta Plasma cell differentiation medicine Humans Smad3 Protein B cell differentiation lcsh:QH301-705.5 Cells Cultured 030304 developmental biology B cells 0303 health sciences DNA methylation CD40 biology Receptors IgE Lymphopoiesis Cell Cycle DNA Cell cycle Molecular biology Repressor Proteins medicine.anatomical_structure lcsh:Biology (General) 030220 oncology & carcinogenesis plasmablast biology.protein 5hmC Positive Regulatory Domain I-Binding Factor 1 Tumor Suppressor Protein p53 |
| Zdroj: | Cell Reports, Vol 13, Iss 5, Pp 1059-1071 (2015) Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname Cell Reports Cell Reports, 2015, 13 (5), pp.1059-1071. ⟨10.1016/j.celrep.2015.09.051⟩ Cell Reports, Elsevier Inc, 2015, 13 (5), pp.1059-1071. ⟨10.1016/j.celrep.2015.09.051⟩ |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.09.051 |
| Popis: | International audience; Molecular mechanisms underlying terminal differentiation of B cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels, but followed by a committal step in which an S phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity. Downregulation of both TGFβ1/SMAD3 signaling and p53 pathway supported this final step, allowing the emergence of a CD23-negative subpopulation in transition from B cells to plasma cells. Remarkably, hydroxymethylation of PRDM1, a gene essential for plasma cell fate, was coupled to progression in S phase, revealing an intricate connection among cell cycle, DNA (hydroxy) methylation, and cell fate determination. |
| Databáze: | OpenAIRE |
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