2025/01/19 by Xiaojuan Zhan, Yi Liu, Yanying Guo +23 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Single-cell and spatial transcriptomics #T-cell and B-cell Immunology #Immunodeficiency and Autoimmune Disorders
paper · doi:10.1101/2025.01.16.630222
openalex publication_date 2025/01/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
Abstract Adaptive immunity, mediated by T and B cell responses, is essential for defending against infections and cancers while also being implicated in autoimmune diseases. Tracking T and B cell repertoires in situ at single-cell resolution is essential for understanding adaptive immune responses. To address the lack of tools for in situ single-cell T/BCR (XCR) sequencing, we developed Stereo-XCR-seq, an efficient strategy for retrieving and sequencing TCR and BCR from Stereo-seq cDNA libraries at subcellular resolution. Stereo-XCR-seq provides unbiased full-length XCR reads alongside spatial transcriptomics, enabling the identification of heterogeneous lymphoid aggregates with distinct clonal activities in cancers and inflammatory bowel disease (IBD). We identified plasma cell aggregates that differ from tertiary lymphoid structures (TLSs) in both transcriptomic profiles and clonal activities, with spatial positioning potentially mediating unique immune responses. Collectively, Stereo-XCR-seq enables in situ single-cell profiling of T and B cell clonal activities within tissue microenvironments, providing insights into lymphocyte adaption to environmental stimuli. This technology provides potential for advancing our understanding of tissue immunity and the development of therapeutic strategies for immune disorders.