Scientific publications

An atlas of cells in the human tonsil. Scientific Publication

Jan 30, 2024 | Magazine: Immunity

Ramon Massoni-Badosa  1 , Sergio Aguilar-Fernández  2 , Juan C Nieto  2 , Paula Soler-Vila  3 , Marc Elosua-Bayes  2 , Domenica Marchese  2 , Marta Kulis  3 , Amaia Vilas-Zornoza  4 , Marco Matteo Bühler  5 , Sonal Rashmi  2 , Clara Alsinet  2 , Ginevra Caratù  2 , Catia Moutinho  2 , Sara Ruiz  2 , Patricia Lorden  2 , Giulia Lunazzi  2 , Dolors Colomer  6 , Gerard Frigola  7 , Will Blevins  2 , Lucia Romero-Rivero  3 , Víctor Jiménez-Martínez  3 , Anna Vidal  3 , Judith Mateos-Jaimez  3 , Alba Maiques-Diaz  3 , Sara Ovejero  8 , Jérôme Moreaux  9 , Sara Palomino  10 , David Gomez-Cabrero  11 , Xabier Agirre  4 , Marc A Weniger  12 , Hamish W King  13 , Lucy C Garner  14 , Federico Marini  15 , Francisco Javier Cervera-Paz  16 , Peter M Baptista  16 , Isabel Vilaseca  17 , Cecilia Rosales  3 , Silvia Ruiz-Gaspà  3 , Benjamin Talks  18 , Keval Sidhpura  19 , Anna Pascual-Reguant  20 , Anja E Hauser  20 , Muzlifah Haniffa  21 , Felipe Prosper  22 , Ralf Küppers  12 , Ivo Glynne Gut  23 , Elias Campo  6 , José Ignacio Martin-Subero  24 , Holger Heyn  25


Abstract

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.

CITATION  Immunity. 2024 Jan 30:S1074-7613(24)00031-1.  doi: 10.1016/j.immuni.2024.01.006