Integrated spatial and multimodal single-cell transcriptomics reveal patient-dependent cell heterogeneity in splenic marginal zone lymphoma.
J Pathol
; 263(4-5): 442-453, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38828498
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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MEDLINE
Asunto principal:
Neoplasias del Bazo
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Linfoma de Células B de la Zona Marginal
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Análisis de la Célula Individual
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Transcriptoma
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2024
Tipo del documento:
Article