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An Atlas of Cells in the Human Tonsil

An Atlas of Cells in the Human Tonsil

来源:bioRxiv_logobioRxiv
英文摘要

Abstract Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we present a comprehensive census of cell types forming the human tonsil by applying single-cell transcriptome, epigenome, proteome and adaptive immune repertoire sequencing as well as spatial transcriptomics, resulting in an atlas of >357,000 cells. We provide a glossary of 121 annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is a reference map to understand alterations observed in disease. Here, we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.

Heyn Holger、Alsinet Clara、Marini Federico、Aguilar-Fern¨¢ndez Sergio、Baptista Peter M.、Elosua-Bayes Marc、Martin-Subero Jos¨| Ignacio、B¨1hler Marco Matteo、Rashmi Sonal、Ruiz Sara、Palomino Sara、Agirre Xabier、Weniger Marc A.、Gut Ivo Glynne、Moutinho Catia、Vilas-Zornoza Amaia、Prosper Felipe、Kulis Marta、Gomez-Cabrero David、Soler-Vila Paula、Cervera-Paz Francisco Javier、Frigola Gerard、Carat¨′ Ginevra、Vilaseca Isabel、Campo Elias、Massoni-Badosa Ramon、Nieto Juan C.、Lunazzi Giulia、K¨1ppers Ralf、Colomer Dolors、Blevins Will、Lorden Patricia、Marchese Domenica

CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)||Universitat Pompeu Fabra (UPF)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz||Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University MainzCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Department of Otorhinolaryngology, University of NavarraCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red C¨¢ncer (CIBERONC)||Departament de Fonaments Cl¨anics, Facultat de Medicina, Universitat de Barcelona||Instituci¨? Catalana de Recerca i Estudis Avan?ats (ICREA)Institut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Department of Pathology and Molecular Pathology, University Hospital Zurich||Hematopathology Section, Pathology department, Hospital ClinicCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Translational Bioinformatics Unit (TransBio), Navarrabiomed, Navarra Health Department (CHN), Public University of Navarra (UPNA), Navarra Institute for Health Research (IdiSNA)Hemato-Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Universidad de Navarra||Centro de Investigaci¨?n Biom¨|dica en Red C¨¢ncer (CIBERONC)Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-EssenCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)||Universitat Pompeu Fabra (UPF)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Hemato-Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Universidad de Navarra||Centro de Investigaci¨?n Biom¨|dica en Red C¨¢ncer (CIBERONC)Hemato-Oncology Program, Center for Applied Medical Research (CIMA), University of Navarra, IDISNA, Universidad de Navarra||Centro de Investigaci¨?n Biom¨|dica en Red C¨¢ncer (CIBERONC)||Departamento de Hematolog¨aa, Cl¨anica Universidad de Navarra, University of NavarraInstitut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)Translational Bioinformatics Unit (TransBio), Navarrabiomed, Navarra Health Department (CHN), Public University of Navarra (UPNA), Navarra Institute for Health Research (IdiSNA)||Bioscience Program, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology KAUSTInstitut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)Department of Otorhinolaryngology, University of NavarraHematopathology Section, Pathology department, Hospital ClinicCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Otorhinolaryngology Head-Neck Surgery Department, Hospital Cl¨anic, IDIBAPS Universitat de BarcelonaInstitut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red C¨¢ncer (CIBERONC)||Hematopathology Section, Pathology department, Hospital Clinic||Departament de Fonaments Cl¨anics, Facultat de Medicina, Universitat de BarcelonaCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-EssenInstitut d?ˉInvestigacions Biom¨¨diques August Pi i Sunyer (IDIBAPS)||Centro de Investigaci¨?n Biom¨|dica en Red C¨¢ncer (CIBERONC)||Hematopathology Section, Pathology department, Hospital Clinic||Departament de Fonaments Cl¨anics, Facultat de Medicina, Universitat de BarcelonaCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST)

10.1101/2022.06.24.497299

基础医学细胞生物学分子生物学

Heyn Holger,Alsinet Clara,Marini Federico,Aguilar-Fern¨¢ndez Sergio,Baptista Peter M.,Elosua-Bayes Marc,Martin-Subero Jos¨| Ignacio,B¨1hler Marco Matteo,Rashmi Sonal,Ruiz Sara,Palomino Sara,Agirre Xabier,Weniger Marc A.,Gut Ivo Glynne,Moutinho Catia,Vilas-Zornoza Amaia,Prosper Felipe,Kulis Marta,Gomez-Cabrero David,Soler-Vila Paula,Cervera-Paz Francisco Javier,Frigola Gerard,Carat¨′ Ginevra,Vilaseca Isabel,Campo Elias,Massoni-Badosa Ramon,Nieto Juan C.,Lunazzi Giulia,K¨1ppers Ralf,Colomer Dolors,Blevins Will,Lorden Patricia,Marchese Domenica.An Atlas of Cells in the Human Tonsil[EB/OL].(2025-03-28)[2025-06-20].https://www.biorxiv.org/content/10.1101/2022.06.24.497299.点此复制

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