Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution
BackgroundDiffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant.MethodsW...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1310292/full |
| _version_ | 1797397484699385856 |
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| author | Fengling Liu Jie Zheng Gaohui Yang Lin Pan Yanni Xie Siyu Chen Jinwei Tuo Jinxia Su Xiuyi Ou Rongrong Liu |
| author_facet | Fengling Liu Jie Zheng Gaohui Yang Lin Pan Yanni Xie Siyu Chen Jinwei Tuo Jinxia Su Xiuyi Ou Rongrong Liu |
| author_sort | Fengling Liu |
| collection | DOAJ |
| description | BackgroundDiffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant.MethodsWe comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments.ResultsOur analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by HMGB3, SAP30, and E2F8, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation.ConclusionsOur research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients. |
| first_indexed | 2024-03-09T01:11:41Z |
| format | Article |
| id | doaj.art-7307d06d92ed4fb2be45ee9c4e726837 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T01:11:41Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7307d06d92ed4fb2be45ee9c4e7268372023-12-11T04:27:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-12-011410.3389/fimmu.2023.13102921310292Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolutionFengling Liu0Jie Zheng1Gaohui Yang2Lin Pan3Yanni Xie4Siyu Chen5Jinwei Tuo6Jinxia Su7Xiuyi Ou8Rongrong Liu9Department of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaDepartment of Hematology, The first Affiliated Hospital of Guangxi Medical University, Nanning, ChinaBackgroundDiffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant.MethodsWe comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments.ResultsOur analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by HMGB3, SAP30, and E2F8, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation.ConclusionsOur research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1310292/fulldiffuse large B cell lymphomacancer stem cellsingle-cell RNA sequencingbulk RNA sequencingtranscription factorimmune escape |
| spellingShingle | Fengling Liu Jie Zheng Gaohui Yang Lin Pan Yanni Xie Siyu Chen Jinwei Tuo Jinxia Su Xiuyi Ou Rongrong Liu Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution Frontiers in Immunology diffuse large B cell lymphoma cancer stem cell single-cell RNA sequencing bulk RNA sequencing transcription factor immune escape |
| title | Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution |
| title_full | Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution |
| title_fullStr | Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution |
| title_full_unstemmed | Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution |
| title_short | Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution |
| title_sort | unraveling the enigma of b cells in diffuse large b cell lymphoma unveiling cancer stem cell like b cell subpopulation at single cell resolution |
| topic | diffuse large B cell lymphoma cancer stem cell single-cell RNA sequencing bulk RNA sequencing transcription factor immune escape |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1310292/full |
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