Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis

Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis

Abstract Richter syndrome (RS), characterized by aggressive lymphoma arising from chronic lymphocytic leukaemia (CLL), presents a poor response to treatment and grim prognosis. To elucidate RS mechanisms, paired samples from a patient with DLBCL-RS were subjected to single-cell RNA sequencing (scRNA...

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Bibliographic Details
Main Authors: Heng Li, Cheng Xing, Ji Li, Yihao Zhan, Ming Luo, Peilong Wang, Yue Sheng, Hongling Peng
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Biomarker Research
Subjects:
Richter syndrome
Chronic lymphocytic leukaemia
scRNA-seq
Chromosome conformation capture sequencing
Hi-C
cAMP-mediated signalling
Online Access:https://doi.org/10.1186/s40364-024-00723-5
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Summary:Abstract Richter syndrome (RS), characterized by aggressive lymphoma arising from chronic lymphocytic leukaemia (CLL), presents a poor response to treatment and grim prognosis. To elucidate RS mechanisms, paired samples from a patient with DLBCL-RS were subjected to single-cell RNA sequencing (scRNA-seq) and high-throughput chromosome conformation capture (Hi-C) sequencing. Over 10,000 cells were profiled via scRNA-seq, revealing the comprehensive B cell transformation in RS. Hi-C sequencing exposed a unique chromatin architecture in RS, with increased proximal and decreased distal interactions. At the compartment scale, the interaction between B compartments was strengthened in DLBCL cells, while topologically associating domains (TADs) in DLBCL had elevated intra-TAD and reduced inter-TAD contacts. Differentially expressed genes at TAD borders between CLL and DLBCL cells highlighted an enrichment of cAMP-mediated signalling. To substantiate the functional relevance of ATF1 and CAP1, the genes involve in cAMP-mediated signalling, in the context of cell proliferation, we have performed gain- and loss-of-function experiments in relevant cell lines. Collectively, integrated scRNA-seq and Hi-C data suggest that chromatin reorganization and altered cAMP signalling drive RS transformation.
ISSN:2050-7771

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