Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing
Abstract Cardiomyopathy encompasses a range of diseases that severely affect the complex functions of the heart, involving structural and functional abnormalities, and is associated with high mortality. Recent studies have highlighted the critical role of ferroptosis in regulating oxidative stress a...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-09928-6 |
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| author | Wenyang Nie Yong Wang Yuanyuan Xiao Zhiheng Lin Jingwen Zhang Zhijie Zhao Zhen Wang |
| author_facet | Wenyang Nie Yong Wang Yuanyuan Xiao Zhiheng Lin Jingwen Zhang Zhijie Zhao Zhen Wang |
| author_sort | Wenyang Nie |
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| description | Abstract Cardiomyopathy encompasses a range of diseases that severely affect the complex functions of the heart, involving structural and functional abnormalities, and is associated with high mortality. Recent studies have highlighted the critical role of ferroptosis in regulating oxidative stress and inflammation in cardiomyopathy. In this study, we established that the C6 S100A4+ SMCs subpopulation is critical by performing an integrated single-cell analysis of the known publicly available data GSE145154. We validated the role of S100A4 in SMCs through in vitro experiments, providing evidence for its potential as a therapeutic target. Furthermore, these cells interact with endothelial cells through the PTN-NCL pathway, influencing disease progression. Key transcription factors, including KLF2, FOS, FOSB, and JUNB, were identified. This key subpopulation, along with its associated signaling pathways, marker genes, stemness genes, and transcription factors, may offer new insights for preventing the onset and progression of cardiomyopathy, particularly ischemic cardiomyopathy. |
| format | Article |
| id | doaj-art-dff76ca20cb0428a97d3fc084ded6274 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dff76ca20cb0428a97d3fc084ded62742025-08-20T03:42:22ZengNature PortfolioScientific Reports2045-23222025-07-0115112510.1038/s41598-025-09928-6Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencingWenyang Nie0Yong Wang1Yuanyuan Xiao2Zhiheng Lin3Jingwen Zhang4Zhijie Zhao5Zhen Wang6First Clinical Medical College, Shandong University of Traditional Chinese MedicineDepartment of Cardiovascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese MedicineDepartment of Ophthalmology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu HospitalDepartment of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Cardiovascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Cardiovascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese MedicineAbstract Cardiomyopathy encompasses a range of diseases that severely affect the complex functions of the heart, involving structural and functional abnormalities, and is associated with high mortality. Recent studies have highlighted the critical role of ferroptosis in regulating oxidative stress and inflammation in cardiomyopathy. In this study, we established that the C6 S100A4+ SMCs subpopulation is critical by performing an integrated single-cell analysis of the known publicly available data GSE145154. We validated the role of S100A4 in SMCs through in vitro experiments, providing evidence for its potential as a therapeutic target. Furthermore, these cells interact with endothelial cells through the PTN-NCL pathway, influencing disease progression. Key transcription factors, including KLF2, FOS, FOSB, and JUNB, were identified. This key subpopulation, along with its associated signaling pathways, marker genes, stemness genes, and transcription factors, may offer new insights for preventing the onset and progression of cardiomyopathy, particularly ischemic cardiomyopathy.https://doi.org/10.1038/s41598-025-09928-6Single-cell RNA sequencingCardiomyopathySmooth muscle cellsFerroptosisExosomesInflammation |
| spellingShingle | Wenyang Nie Yong Wang Yuanyuan Xiao Zhiheng Lin Jingwen Zhang Zhijie Zhao Zhen Wang Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing Scientific Reports Single-cell RNA sequencing Cardiomyopathy Smooth muscle cells Ferroptosis Exosomes Inflammation |
| title | Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing |
| title_full | Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing |
| title_fullStr | Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing |
| title_full_unstemmed | Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing |
| title_short | Identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single-cell RNA sequencing |
| title_sort | identification of a key smooth muscle cell subset driving ischemic cardiomyopathy progression through single cell rna sequencing |
| topic | Single-cell RNA sequencing Cardiomyopathy Smooth muscle cells Ferroptosis Exosomes Inflammation |
| url | https://doi.org/10.1038/s41598-025-09928-6 |
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