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    Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

    Citation

    Ramon Massoni-Badosa, Sergio Aguilar-Fernández, Juan C Nieto, Paula Soler-Vila, Marc Elosua-Bayes, Domenica Marchese, Marta Kulis, Amaia Vilas-Zornoza, Marco Matteo Bühler, Sonal Rashmi, Clara Alsinet, Ginevra Caratù, Catia Moutinho, Sara Ruiz, Patricia Lorden, Giulia Lunazzi, Dolors Colomer, Gerard Frigola, Will Blevins, Lucia Romero-Rivero, Víctor Jiménez-Martínez, Anna Vidal, Judith Mateos-Jaimez, Alba Maiques-Diaz, Sara Ovejero, Jérôme Moreaux, Sara Palomino, David Gomez-Cabrero, Xabier Agirre, Marc A Weniger, Hamish W King, Lucy C Garner, Federico Marini, Francisco Javier Cervera-Paz, Peter M Baptista, Isabel Vilaseca, Cecilia Rosales, Silvia Ruiz-Gaspà, Benjamin Talks, Keval Sidhpura, Anna Pascual-Reguant, Anja E Hauser, Muzlifah Haniffa, Felipe Prosper, Ralf Küppers, Ivo Glynne Gut, Elias Campo, José Ignacio Martin-Subero, Holger Heyn. An atlas of cells in the human tonsil. Immunity. 2024 Feb 13;57(2):379-399.e18

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    PMID: 38301653

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