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Updated: May 5, 2026
Single-cell Gene Expression Using Multiplex RT-qPCR to Characterize Heterogeneity of Rare Lymphoid Populations
Published on: January 19, 2017
Integrated spatial and multimodal single-cell transcriptomics reveal patient-dependent cell heterogeneity in splenic
Juan Pablo Cerapio1,2,3, Pauline Gravelle1,2,3,4,5, Anne Quillet-Mary1,2,3,4
1Université de Toulouse, INSERM UMR1037, CNRS UMR5071, Université Toulouse III-Paul Sabatier, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.
Insights
This study reveals splenic marginal zone lymphoma (SMZL) cells exhibit desynchronized B-cell maturation between the spleen and blood. T-follicular helper cell interactions are key in the nodular SMZL subtype.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Biological hallmarks of splenic marginal zone lymphoma (SMZL) are not well understood.
- Comprehensive characterization of SMZL requires advanced molecular profiling techniques.
Purpose of the Study:
- To perform in-depth characterization of SMZL using multimodal single-cell analyses.
- To elucidate the heterogeneity and biological mechanisms underlying SMZL.
Main Methods:
- Integration of 3'-single-cell RNA-sequencing, Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), and 5'-V(D)J single-cell RNA-sequencing.
- Spatial transcriptomics and imaging mass cytometry were employed for in situ analysis.
Main Results:
- SMZL B-cell clones in the spleen are memory-like, while blood B-cells show diverse differentiation stages, indicating desynchronized maturation.
- Nodular SMZL subtypes show enrichment of T-effector and T-follicular helper (TFH) signatures.
- Evidence of dynamic crosstalk between TFH cells and cancer cells was observed.
Conclusions:
- This study provides a high-resolution description of SMZL biological hallmarks.
- First in situ characterization of inter- and intra-patient heterogeneity in SMZL at transcriptomic and protein levels.
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.
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