Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC
IntroductionThe role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed.MethodsTo investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patient...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1494025/full |
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| author | Xiyu Song Xiyu Song Xiyu Song Jianhua Jiao Jianhua Jiao Jiayang Qin Wei Zhang Weijun Qin Weijun Qin Shuaijun Ma Shuaijun Ma |
| author_facet | Xiyu Song Xiyu Song Xiyu Song Jianhua Jiao Jianhua Jiao Jiayang Qin Wei Zhang Weijun Qin Weijun Qin Shuaijun Ma Shuaijun Ma |
| author_sort | Xiyu Song |
| collection | DOAJ |
| description | IntroductionThe role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed.MethodsTo investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patients, integrating both single-cell sequencing and bulk tissue sequencing data from online sequencing databases, followed by validation via spatial transcriptomics and multiplex immunohistochemistry (mIHC).ResultsWe identified four MC signature genes (TPSB2, TPSAB1, CPA3, and HPGDS). MC density was significantly greater in ccRCC tissues than in normal tissues, but MC activation characteristics were not significantly different between ccRCC and normal tissues. Activated and resting MCs were defined as having high and low expression of MC receptors and mediators, respectively, whereas proliferating MCs had high expression of proliferation-related genes. The overall percentage of activated MCs in ccRCC tissues did not change significantly but shifted toward a more activated subpopulation (VEGFA+ MCs), with a concomitant decrease in proliferative MCs (TNF+ MCs) and resting MCs. An analysis of the ratio of TNF+/VEGFA+ MCs in tumors revealed that MCs exerted antitumor effects on ccRCC. However, VEGFA+MC was produced in large quantities in ccRCC tissues and promoted tumor angiogenesis compared with adjacent normal tissues, which aroused our concern. In addition, MC signature genes were associated with a better prognosis in the KIRC patient cohort in the TCGA database, which is consistent with our findings. Furthermore, the highest level of IL1B expression was observed in macrophages in ccRCC samples, and spatial transcriptome analysis revealed the colocalization of VEGFA+ MCs with IL1B+ macrophages at the tumor–normal interface.DiscussionIn conclusion, this study revealed increased MC density in ccRCC. Although the proportion of activated MCs was not significantly altered in ccRCC tissues compared with normal tissues, this finding highlights a shift in the MC phenotype from CTSGhighMCs to more activated VEGFA+MCs, providing a potential therapeutic target for inhibiting ccRCC progression. |
| format | Article |
| id | doaj-art-adad4d792a03483f9c262b5e7edd6c73 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-adad4d792a03483f9c262b5e7edd6c732025-01-07T06:47:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14940251494025Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCCXiyu Song0Xiyu Song1Xiyu Song2Jianhua Jiao3Jianhua Jiao4Jiayang Qin5Wei Zhang6Weijun Qin7Weijun Qin8Shuaijun Ma9Shuaijun Ma10Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, Shaanxi, ChinaXijing Innovation Research Institute, Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, ChinaXijing Innovation Research Institute, Fourth Military Medical University, Xi’an, Shaanxi, ChinaWest China School of Medicine, West China Hospital, Sichuan University, Chengdu, ChinaNational Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, ChinaXijing Innovation Research Institute, Fourth Military Medical University, Xi’an, Shaanxi, ChinaDepartment of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, ChinaXijing Innovation Research Institute, Fourth Military Medical University, Xi’an, Shaanxi, ChinaIntroductionThe role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed.MethodsTo investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patients, integrating both single-cell sequencing and bulk tissue sequencing data from online sequencing databases, followed by validation via spatial transcriptomics and multiplex immunohistochemistry (mIHC).ResultsWe identified four MC signature genes (TPSB2, TPSAB1, CPA3, and HPGDS). MC density was significantly greater in ccRCC tissues than in normal tissues, but MC activation characteristics were not significantly different between ccRCC and normal tissues. Activated and resting MCs were defined as having high and low expression of MC receptors and mediators, respectively, whereas proliferating MCs had high expression of proliferation-related genes. The overall percentage of activated MCs in ccRCC tissues did not change significantly but shifted toward a more activated subpopulation (VEGFA+ MCs), with a concomitant decrease in proliferative MCs (TNF+ MCs) and resting MCs. An analysis of the ratio of TNF+/VEGFA+ MCs in tumors revealed that MCs exerted antitumor effects on ccRCC. However, VEGFA+MC was produced in large quantities in ccRCC tissues and promoted tumor angiogenesis compared with adjacent normal tissues, which aroused our concern. In addition, MC signature genes were associated with a better prognosis in the KIRC patient cohort in the TCGA database, which is consistent with our findings. Furthermore, the highest level of IL1B expression was observed in macrophages in ccRCC samples, and spatial transcriptome analysis revealed the colocalization of VEGFA+ MCs with IL1B+ macrophages at the tumor–normal interface.DiscussionIn conclusion, this study revealed increased MC density in ccRCC. Although the proportion of activated MCs was not significantly altered in ccRCC tissues compared with normal tissues, this finding highlights a shift in the MC phenotype from CTSGhighMCs to more activated VEGFA+MCs, providing a potential therapeutic target for inhibiting ccRCC progression.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1494025/fullmast cellclear cell renal cell carcinomasingle-cell RNA sequencingheterogeneityspatial transcriptomicsprognosis |
| spellingShingle | Xiyu Song Xiyu Song Xiyu Song Jianhua Jiao Jianhua Jiao Jiayang Qin Wei Zhang Weijun Qin Weijun Qin Shuaijun Ma Shuaijun Ma Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC Frontiers in Immunology mast cell clear cell renal cell carcinoma single-cell RNA sequencing heterogeneity spatial transcriptomics prognosis |
| title | Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC |
| title_full | Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC |
| title_fullStr | Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC |
| title_full_unstemmed | Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC |
| title_short | Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC |
| title_sort | single cell transcriptomics reveals the heterogeneity and function of mast cells in human ccrcc |
| topic | mast cell clear cell renal cell carcinoma single-cell RNA sequencing heterogeneity spatial transcriptomics prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1494025/full |
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