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circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics

  • Izabela Plumbom,
  • Benedikt Obermayer,
  • Raphael Raspe,
  • Anna Pascual-Reguant,
  • Ilan Theurillat,
  • Tancredi Massimo Pentimalli,
  • Yu-Hsin Hsieh,
  • Marine Gil,
  • Carola Dietrich,
  • Michaela Seeger-Zografakis,
  • Claudia Quedenau,
  • Jeannine Wilde,
  • Caroline Braeuning,
  • Cornelius Fischer,
  • Markus Schuelke,
  • Volkhard Seitz,
  • Leif S. Ludwig,
  • Angelika Eggert,
  • Nikolaus Rajewsky,
  • Tatiana Borodina,
  • Dieter Beule,
  • Janine Altmueller,
  • Helena Radbruch,
  • Anja Erika Hauser,
  • Thomas Conrad

摘要

Monitoring T cell repertoires in human tissues provides important insights into immune response mechanisms in cancer, infectious diseases, and autoimmunity. However, retrieving VDJ information from single-cell and spatial transcriptomics workflows with 3’-barcoding of cDNA remains resource-intensive or requires specialized sequencing equipment. Here, we introduce circVDJ-seq for simplified and cost-efficient T cell receptor (TCR) profiling from 3’-directed workflows like single-cell or single-nucleus RNA sequencing, ATAC + RNA multi-omics, and spatial transcriptomics. Application of circVDJ-seq to freshly resected neuroblastomas and postmortem lymph nodes affected by pneumonia or COVID-19 reveals distinct immune microenvironments and T cell clonality patterns, highlighting broad utility across diverse clinical contexts.