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. 2024 Aug;263(4-5):442-453.
doi: 10.1002/path.6296. Epub 2024 Jun 3.

Integrated spatial and multimodal single-cell transcriptomics reveal patient-dependent cell heterogeneity in splenic marginal zone lymphoma

Juan Pablo Cerapio #  1   2   3 , Pauline Gravelle #  1   2   3   4   5 , Anne Quillet-Mary  1   2   3   4 , Carine Valle  1   2   3 , Frederic Martins  6 , Don-Marc Franchini  1   2   3   4   5 , Charlotte Syrykh  1   5 , Pierre Brousset  1   2   3   4   5 , Alexandra Traverse-Glehen  7 , Loic Ysebaert  1   2   3   4   5 , Jean-Jacques Fournie  1   2   3   4 , Camille Laurent  1   2   3   4   5
Affiliations

Integrated spatial and multimodal single-cell transcriptomics reveal patient-dependent cell heterogeneity in splenic marginal zone lymphoma

Juan Pablo Cerapio et al. J Pathol. 2024 Aug.

Abstract

Biological hallmarks of splenic marginal zone lymphoma (SMZL) remain poorly described. Herein, we performed in-depth SMZL characterization through multimodal single-cell analyses of paired blood/spleen samples. The 3'-single-cell RNA-sequencing, Cellular Indexing of Transcriptomes and Epitopes by sequencing, and 5'-V(D)J single-cell RNA-sequencing datasets were integrated to characterize SMZL transcriptome profiles, including B-cell receptor and T-cell receptor repertoires. Hyperexpanded B-cell clones in the spleen were at a memory-like stage, whereas recirculating tumor B-cells in blood encompassed multiple differentiation stages, indicating an unexpected desynchronization of the B-cell maturation program in SMZL cells. Spatial transcriptomics showed the enrichment of T-effector and T-follicular helper (TFH) signatures in the nodular subtype of SMZL. This latter also exhibited gene-based cell-cell interactions suggestive of dynamic crosstalk between TFH and cancer cells in transcriptomics, further substantiated by using imaging mass cytometry. Our findings provide a comprehensive high-resolution description of SMZL biological hallmarks and characterize, for the first time in situ, inter- and intra-patient heterogeneity at both transcriptomic and protein levels. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: lymphoma; microenvironment; multimodal omics; single‐cell RNA‐sequencing; spatial transcriptomics.

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