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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BMC
2025-01-01
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| Series: | Biomarker Research |
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| Online Access: | https://doi.org/10.1186/s40364-024-00723-5 |
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| author | Heng Li Cheng Xing Ji Li Yihao Zhan Ming Luo Peilong Wang Yue Sheng Hongling Peng |
| author_facet | Heng Li Cheng Xing Ji Li Yihao Zhan Ming Luo Peilong Wang Yue Sheng Hongling Peng |
| author_sort | Heng Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f54514439145444fb0084b6febc14150 |
| institution | Kabale University |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Biomarker Research |
| spelling | doaj-art-f54514439145444fb0084b6febc141502025-01-26T12:45:40ZengBMCBiomarker Research2050-77712025-01-011311510.1186/s40364-024-00723-5Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysisHeng Li0Cheng Xing1Ji Li2Yihao Zhan3Ming Luo4Peilong Wang5Yue Sheng6Hongling Peng7Department of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of General Surgery, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityDepartment of Hematology, The Second Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1186/s40364-024-00723-5Richter syndromeChronic lymphocytic leukaemiascRNA-seqChromosome conformation capture sequencingHi-CcAMP-mediated signalling |
| spellingShingle | Heng Li Cheng Xing Ji Li Yihao Zhan Ming Luo Peilong Wang Yue Sheng Hongling Peng Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis Biomarker Research Richter syndrome Chronic lymphocytic leukaemia scRNA-seq Chromosome conformation capture sequencing Hi-C cAMP-mediated signalling |
| title | Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis |
| title_full | Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis |
| title_fullStr | Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis |
| title_full_unstemmed | Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis |
| title_short | Aberrant c-AMP signalling in richter syndrome revealed by single-cell transcriptome and 3D chromatin analysis |
| title_sort | aberrant c amp signalling in richter syndrome revealed by single cell transcriptome and 3d chromatin analysis |
| topic | Richter syndrome Chronic lymphocytic leukaemia scRNA-seq Chromosome conformation capture sequencing Hi-C cAMP-mediated signalling |
| url | https://doi.org/10.1186/s40364-024-00723-5 |
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