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Updated: Jul 6, 2026
Single Cell Transcriptional Profiling of Adult Mouse Cardiomyocytes
Published on: December 28, 2011
Identification of senescence related hub genes and potential therapeutic compounds for dilated cardiomyopathy via
Chong Du1, Sibo Wang1, Xinying Shi1
1Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Background:
Dilated cardiomyopathy (DCM) is a common cause of heart failure. However, the role of cellular senescence in DCM has not been fully elucidated. Here, we aimed to investigate senescence in DCM, identify senescence related characteristic genes, and explore the potential small molecule compounds for DCM treatment.
Methods:
DCM-associated datasets and senescence-related genes were respectively obtained from Gene Expression Omnibus (GEO) database and CellAge database. The characteristic genes were identified through methods including weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and random forest. The expression of characteristic genes was verified in the mouse DCM model. Moreover, the CIBERSORT algorithm was applied to analyze immune characteristics of DCM. Finally, several therapeutic compounds were predicted by CMap analysis, and the potential mechanism of chlorogenic acid (CGA) was investigated by molecular docking and molecular dynamics simulation.
Results:
Three DCM- and senescence-related characteristic genes (MME, GNMT and PLA2G2A) were ultimately identified through comprehensive transcriptome analysis, and were experimentally verified in the doxorubicin induced mouse DCM. Meanwhile, the established diagnostic model, derived from dataset analysis, showed ideal diagnostic performance for DCM. Immune cell infiltration analysis suggested dysregulation of inflammation in DCM, and the characteristic genes were significantly associated with invasive immune cells. Finally, based on the specific gene expression profile of DCM, several potential therapeutic compounds were predicted through CMap analysis. In addition, molecular docking and molecular dynamics simulations suggested that CGA could bind to the active pocket of MME protein.
Conclusion:
Our study presents three characteristic genes (MME, PLA2G2A, and GNMT) and a novel senescence-based diagnostic nomogram, and discusses potential therapeutic compounds, providing new insights into the diagnosis and treatment of DCM.
Insights
This study identifies three key genes (MME, PLA2G2A, GNMT) linked to cellular senescence in dilated cardiomyopathy (DCM) and proposes potential treatments for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Aging Research
Background:
- Dilated cardiomyopathy (DCM) is a significant cause of heart failure, but the role of cellular senescence remains unclear.
- Investigating cellular senescence in DCM is crucial for understanding disease mechanisms and developing new therapies.
Purpose of the Study:
- To investigate cellular senescence in DCM.
- To identify characteristic genes associated with senescence in DCM.
- To explore potential small molecule compounds for DCM treatment.
Main Methods:
- Utilized DCM datasets and senescence-related genes from public databases.
- Employed WGCNA, LASSO, and random forest for characteristic gene identification.
- Validated gene expression in a mouse DCM model and analyzed immune cell infiltration.
- Predicted therapeutic compounds using CMap analysis and investigated chlorogenic acid (CGA) mechanism.
Main Results:
- Identified and experimentally verified three key genes (MME, GNMT, PLA2G2A) related to DCM and senescence.
- Developed a diagnostic model with high performance for DCM.
- Revealed immune cell dysregulation and inflammation in DCM, linking characteristic genes to invasive immune cells.
- Predicted potential therapeutic compounds, with CGA showing binding affinity to MME protein.
Conclusions:
- Identified three characteristic genes (MME, PLA2G2A, GNMT) and a novel senescence-based diagnostic nomogram for DCM.
- Provided new insights into DCM diagnosis and treatment through the identification of potential therapeutic compounds.
- Highlighted the significant role of cellular senescence in the pathogenesis of dilated cardiomyopathy.
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