An atlas of cells in the human tonsil.

Human Cell Atlas adaptive immunity aging human tonsil innate immunity mantle cell lymphoma secondary lymphoid organs single-cell genomics spatial transcriptomics

Journal

Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918

Informations de publication

Date de publication:
30 Jan 2024
Historique:
received: 28 06 2022
revised: 07 07 2023
accepted: 09 01 2024
medline: 2 2 2024
pubmed: 2 2 2024
entrez: 1 2 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 38301653
pii: S1074-7613(24)00031-1
doi: 10.1016/j.immuni.2024.01.006
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests H.H. is co-founder of Omniscope, SAB member of Nanostring and MiRXES, and consultant to Moderna and Singularity. J.C.N. is consultant to Omniscope.

Auteurs

Ramon Massoni-Badosa (R)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain. Electronic address: ram4025@med.cornell.edu.

Sergio Aguilar-Fernández (S)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Juan C Nieto (JC)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Paula Soler-Vila (P)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Marc Elosua-Bayes (M)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Domenica Marchese (D)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Marta Kulis (M)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Amaia Vilas-Zornoza (A)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.

Marco Matteo Bühler (MM)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland; Hematopathology Section, Pathology Department, Hospital Clinic, Barcelona, Spain.

Sonal Rashmi (S)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Clara Alsinet (C)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Ginevra Caratù (G)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Catia Moutinho (C)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Sara Ruiz (S)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Patricia Lorden (P)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Giulia Lunazzi (G)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Dolors Colomer (D)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain; Hematopathology Section, Pathology Department, Hospital Clinic, Barcelona, Spain; Departament de Fonaments Clínics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.

Gerard Frigola (G)

Hematopathology Section, Pathology Department, Hospital Clinic, Barcelona, Spain.

Will Blevins (W)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain.

Lucia Romero-Rivero (L)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Víctor Jiménez-Martínez (V)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Anna Vidal (A)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Judith Mateos-Jaimez (J)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Alba Maiques-Diaz (A)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Sara Ovejero (S)

Department of Biological Hematology, CHU Montpellier, Montpellier, France; Institute of Human Genetics, UMR 9002 CNRS-UM, Montpellier, France.

Jérôme Moreaux (J)

Department of Biological Hematology, CHU Montpellier, Montpellier, France; Institute of Human Genetics, UMR 9002 CNRS-UM, Montpellier, France; Department of Clinical Hematology, CHU Montpellier, Montpellier, France.

Sara Palomino (S)

Translational Bioinformatics Unit (TransBio), Navarrabiomed, Navarra Health Department (CHN), Public University of Navarra (UPNA), Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.

David Gomez-Cabrero (D)

Translational Bioinformatics Unit (TransBio), Navarrabiomed, Navarra Health Department (CHN), Public University of Navarra (UPNA), Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Bioscience Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUST, Thuwal, Saudi Arabia.

Xabier Agirre (X)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.

Marc A Weniger (MA)

Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.

Hamish W King (HW)

Epigenetics and Development Division, Walter and Eliza Hall Institute, Parkville, Australia.

Lucy C Garner (LC)

Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Federico Marini (F)

Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Francisco Javier Cervera-Paz (FJ)

Department of Otorhinolaryngology, University of Navarra, Pamplona, Spain.

Peter M Baptista (PM)

Department of Otorhinolaryngology, University of Navarra, Pamplona, Spain.

Isabel Vilaseca (I)

Otorhinolaryngology Head-Neck Surgery Department, Hospital Clínic, IDIBAPS Universitat de Barcelona, Barcelona, Spain.

Cecilia Rosales (C)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Silvia Ruiz-Gaspà (S)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Benjamin Talks (B)

Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK; Department of Otolaryngology, Freeman Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.

Keval Sidhpura (K)

Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK.

Anna Pascual-Reguant (A)

Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin, Germany.

Anja E Hauser (AE)

Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany; Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin, Germany.

Muzlifah Haniffa (M)

Biosciences Institute, Newcastle University, Newcastle Upon Tyne, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.

Felipe Prosper (F)

Hemato-Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain; Departamento de Hematología, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.

Ralf Küppers (R)

Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.

Ivo Glynne Gut (IG)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.

Elias Campo (E)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain; Hematopathology Section, Pathology Department, Hospital Clinic, Barcelona, Spain; Departament de Fonaments Clínics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.

José Ignacio Martin-Subero (JI)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Departament de Fonaments Clínics, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Electronic address: imartins@recerca.clinic.cat.

Holger Heyn (H)

Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: holger.heyn@cnag.eu.

Classifications MeSH