Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing
Abstract Background Primary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the i...
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Wiley
2024-12-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.70113 |
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| author | Jingyuan Huo Zhen Wang Wenting Zhao Miao Chen Haoyang Li Fengpu He Xiao Tian Yaqi Ma Firyuza Husanova Liang Ma Yiming Ni Hongda Ding Weidong Li Hongfei Xu |
| author_facet | Jingyuan Huo Zhen Wang Wenting Zhao Miao Chen Haoyang Li Fengpu He Xiao Tian Yaqi Ma Firyuza Husanova Liang Ma Yiming Ni Hongda Ding Weidong Li Hongfei Xu |
| author_sort | Jingyuan Huo |
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| description | Abstract Background Primary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the intratumoural heterogeneity and TME diversity of PCAS using single‐cell RNA sequencing (scRNA‐seq). Methods We performed scRNA‐seq analysis on tumour samples from four patients with PCAS, supplemented with multicolour immunohistochemistry for identification. We used scRNA‐seq data from five normal cardiac tissue samples downloaded from public databases for comparative analyses. Bioinformatic analyses, including Cell Ranger, Seurat, Monocle2, hdWGCNA, SCENIC and NicheNet, were utilized to identify distinct cell populations, transcriptional patterns, and co‐regulating gene modules. Results Our analysis revealed significant intratumoural heterogeneity in PCAS driven by diverse biological processes such as protein synthesis, degradation, and RIG‐I signalling inhibition. The SCENIC analysis identified three primary transcription factors' clusters (CEBPB, MYC and TAL1). T‐cell subset analysis showed exhausted antigen‐specific T‐cells, complicating the efficacy of immune checkpoint blockade. Furthermore, we observed suppressive macrophages (SPP1+ and OLR1+) and reduced mitochondrial gene MT‐RNR2 (MTRNR2L12) expression in TME‐infiltrating cells, indicating impaired mitochondrial function. Conclusion This study elucidates the complex cellular landscape and immune microenvironment of PCAS, highlighting potential molecular targets for the development of novel therapies. These findings underscore the importance of a multifaceted therapeutic approach for addressing the challenges posed by PCAS's heterogeneity and immune evasion. Key points Insights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities. Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages). Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting. |
| format | Article |
| id | doaj-art-dc87586e225b45529c35f49ea20ec565 |
| institution | Kabale University |
| issn | 2001-1326 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
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| series | Clinical and Translational Medicine |
| spelling | doaj-art-dc87586e225b45529c35f49ea20ec5652025-01-30T03:56:55ZengWileyClinical and Translational Medicine2001-13262024-12-011412n/an/a10.1002/ctm2.70113Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencingJingyuan Huo0Zhen Wang1Wenting Zhao2Miao Chen3Haoyang Li4Fengpu He5Xiao Tian6Yaqi Ma7Firyuza Husanova8Liang Ma9Yiming Ni10Hongda Ding11Weidong Li12Hongfei Xu13Department of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiology School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Pathology School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of General Surgery Shengjing Hospital of China Medical University Shenyang ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaDepartment of Cardiovascular Surgery School of Medicine the First Affiliated Hospital of Zhejiang University Hangzhou ChinaAbstract Background Primary cardiac angiosarcoma (PCAS) is a rare and aggressive heart tumour with limited treatment options and a poor prognosis. Understanding cellular heterogeneity and tumour microenvironment (TME) is crucial for the development of effective therapies. Here, we investigated the intratumoural heterogeneity and TME diversity of PCAS using single‐cell RNA sequencing (scRNA‐seq). Methods We performed scRNA‐seq analysis on tumour samples from four patients with PCAS, supplemented with multicolour immunohistochemistry for identification. We used scRNA‐seq data from five normal cardiac tissue samples downloaded from public databases for comparative analyses. Bioinformatic analyses, including Cell Ranger, Seurat, Monocle2, hdWGCNA, SCENIC and NicheNet, were utilized to identify distinct cell populations, transcriptional patterns, and co‐regulating gene modules. Results Our analysis revealed significant intratumoural heterogeneity in PCAS driven by diverse biological processes such as protein synthesis, degradation, and RIG‐I signalling inhibition. The SCENIC analysis identified three primary transcription factors' clusters (CEBPB, MYC and TAL1). T‐cell subset analysis showed exhausted antigen‐specific T‐cells, complicating the efficacy of immune checkpoint blockade. Furthermore, we observed suppressive macrophages (SPP1+ and OLR1+) and reduced mitochondrial gene MT‐RNR2 (MTRNR2L12) expression in TME‐infiltrating cells, indicating impaired mitochondrial function. Conclusion This study elucidates the complex cellular landscape and immune microenvironment of PCAS, highlighting potential molecular targets for the development of novel therapies. These findings underscore the importance of a multifaceted therapeutic approach for addressing the challenges posed by PCAS's heterogeneity and immune evasion. Key points Insights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities. Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages). Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting.https://doi.org/10.1002/ctm2.70113heterogeneitymulticolour immunohistochemistryprimary cardiac angiosarcomasingle‐cell RNA sequencingtumour microenvironment |
| spellingShingle | Jingyuan Huo Zhen Wang Wenting Zhao Miao Chen Haoyang Li Fengpu He Xiao Tian Yaqi Ma Firyuza Husanova Liang Ma Yiming Ni Hongda Ding Weidong Li Hongfei Xu Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing Clinical and Translational Medicine heterogeneity multicolour immunohistochemistry primary cardiac angiosarcoma single‐cell RNA sequencing tumour microenvironment |
| title | Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing |
| title_full | Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing |
| title_fullStr | Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing |
| title_full_unstemmed | Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing |
| title_short | Investigating intra‐tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single‐cell RNA sequencing |
| title_sort | investigating intra tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single cell rna sequencing |
| topic | heterogeneity multicolour immunohistochemistry primary cardiac angiosarcoma single‐cell RNA sequencing tumour microenvironment |
| url | https://doi.org/10.1002/ctm2.70113 |
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