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Integrative single-cell chromatin and transcriptome analysis of human plasma cell differentiation.
Alaterre, Elina; Ovejero, Sara; Bret, Caroline; Dutrieux, Laure; Sika, Dassou; Fernandez Perez, Raul; Espéli, Marion; Fest, Thierry; Cogné, Michel; Martin-Subero, José Ignacio; Milpied, Pierre; Cavalli, Giacomo; Moreaux, Jérôme.
Afiliación
  • Alaterre E; Institute of Human Genetics, Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Université Montpellier, Montpellier, France.
  • Ovejero S; Institute of Human Genetics, Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Université Montpellier, Montpellier, France.
  • Bret C; Department of Biological Hematology, CHU Montpellier, Montpellier, France.
  • Dutrieux L; Institute of Human Genetics, Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Université Montpellier, Montpellier, France.
  • Sika D; Department of Biological Hematology, CHU Montpellier, Montpellier, France.
  • Fernandez Perez R; Institute of Human Genetics, Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Université Montpellier, Montpellier, France.
  • Espéli M; Institute of Human Genetics, Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Université Montpellier, Montpellier, France.
  • Fest T; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
  • Cogné M; INSERM U1160 EMiLy, Institut de Recherche Saint-Louis, Université Paris-Cité, Paris, France.
  • Martin-Subero JI; Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, Team B_DEVIL, UMR_S1236, Rennes, France.
  • Milpied P; Laboratoire d'Hématologie, Centre Hospitalier Universitaire, Rennes, France.
  • Cavalli G; Institut National de La Santé et de La Recherche Médicale, Unité Mixte de Recherche U1236, Université de Rennes, Etablissement Français Du Sang Bretagne, Rennes, France.
  • Moreaux J; Centre Hospitalier Universitaire de Rennes, Suivi Immunologique des Thérapies Innovantes, Pôle Biologie, Rennes, France.
Blood ; 144(5): 496-509, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-38643512
ABSTRACT
ABSTRACT Plasma cells (PCs) are highly specialized cells representing the end stage of B-cell differentiation. We have shown that PC differentiation can be reproduced in vitro using elaborate culture systems. The molecular changes occurring during PC differentiation are recapitulated in this in vitro differentiation model. However, a major challenge exists to decipher the spatiotemporal epigenetic and transcriptional programs that drive the early stages of PC differentiation. We combined single cell (sc) RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high throughput sequencing (scATAC-seq) to decipher the trajectories involved in PC differentiation. ScRNA-seq experiments revealed a strong heterogeneity of the preplasmablastic and plasmablastic stages. Among genes that were commonly identified using scATAC-seq and scRNA-seq, we identified several transcription factors with significant stage specific potential importance in PC differentiation. Interestingly, differentially accessible peaks characterizing the preplasmablastic stage were enriched in motifs of BATF3, FOS and BATF, belonging to activating protein 1 (AP-1) transcription factor family that may represent key transcriptional nodes involved in PC differentiation. Integration of transcriptomic and epigenetic data at the single cell level revealed that a population of preplasmablasts had already undergone epigenetic remodeling related to PC profile together with unfolded protein response activation and are committed to differentiate in PC. These results and the supporting data generated with our in vitro PC differentiation model provide a unique resource for the identification of molecular circuits that are crucial for early and mature PC maturation and biological functions. These data thus provide critical insights into epigenetic- and transcription-mediated reprogramming events that sustain PC differentiation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Plasmáticas / Cromatina / Diferenciación Celular / Perfilación de la Expresión Génica / Análisis de la Célula Individual Límite: Humans Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Plasmáticas / Cromatina / Diferenciación Celular / Perfilación de la Expresión Génica / Análisis de la Célula Individual Límite: Humans Idioma: En Revista: Blood Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos