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.
Competing Interest Statement
H.H. is co-founder of Omniscope and scientific advisory board member of MiRXES.
Footnotes
↵19 Senior authors
↵20 Lead contact
https://github.com/Single-Cell-Genomics-Group-CNAG-CRG/TonsilAtlas
https://singlecellgenomics-cnag-crg.shinyapps.io/Annotation/
https://github.com/Single-Cell-Genomics-Group-CNAG-CRG/shiny-pathology
https://github.com/iSEE/iSEE_instances/tree/master/iSEE_HCATonsilData