Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy
Abstract Background Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced sin...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-023-01540-2 |
| _version_ | 1797863569040080896 |
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| author | Jie Xiong Zhaoyue Li Hao Tang Yuchen Duan Xiaofang Ban Ke Xu Yutong Guo Yingfeng Tu |
| author_facet | Jie Xiong Zhaoyue Li Hao Tang Yuchen Duan Xiaofang Ban Ke Xu Yutong Guo Yingfeng Tu |
| author_sort | Jie Xiong |
| collection | DOAJ |
| description | Abstract Background Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study. Results Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8+ T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4+ CD28null T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2- SPP1+ foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses. Conclusions We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies. |
| first_indexed | 2024-04-09T22:37:37Z |
| format | Article |
| id | doaj.art-df0a07c73e714b4f9bb9d633678837bb |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-09T22:37:37Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-df0a07c73e714b4f9bb9d633678837bb2023-03-22T12:22:54ZengBMCBMC Biology1741-70072023-02-0121112310.1186/s12915-023-01540-2Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapyJie Xiong0Zhaoyue Li1Hao Tang2Yuchen Duan3Xiaofang Ban4Ke Xu5Yutong Guo6Yingfeng Tu7Department of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Harbin Medical UniversityAbstract Background Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study. Results Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8+ T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4+ CD28null T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2- SPP1+ foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses. Conclusions We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies.https://doi.org/10.1186/s12915-023-01540-2AtherosclerosisSingle-cell RNA sequencingImmune cellsHeterogeneityImmunotherapy |
| spellingShingle | Jie Xiong Zhaoyue Li Hao Tang Yuchen Duan Xiaofang Ban Ke Xu Yutong Guo Yingfeng Tu Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy BMC Biology Atherosclerosis Single-cell RNA sequencing Immune cells Heterogeneity Immunotherapy |
| title | Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy |
| title_full | Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy |
| title_fullStr | Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy |
| title_full_unstemmed | Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy |
| title_short | Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy |
| title_sort | bulk and single cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy |
| topic | Atherosclerosis Single-cell RNA sequencing Immune cells Heterogeneity Immunotherapy |
| url | https://doi.org/10.1186/s12915-023-01540-2 |
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