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Technical Applications of Microelectrode Array and Patch Clamp Recordings on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: August 4, 2022
Bioinformatics method identifies potential biomarkers of dilated cardiomyopathy in a human induced pluripotent stem
Yu Zhuang1, Yu-Jia Gong2, Bei-Fen Zhong3
1Department of Cardiovascular Surgery, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Insights
Dilated cardiomyopathy (DCM) involves molecular mechanisms in blood vessel development and cell adhesion. Researchers identified potential biomarkers including MMP2, FLT1, CDH1, and others for early detection of this common heart failure cause.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genomics
Background:
- Dilated cardiomyopathy (DCM) is the most prevalent cardiomyopathy, significantly contributing to heart failure cases.
- Understanding the molecular underpinnings of DCM is crucial for developing diagnostic and therapeutic strategies.
Purpose of the Study:
- To elucidate the molecular mechanisms driving DCM.
- To identify potential biomarkers for the early detection of DCM.
Main Methods:
- Utilized a public dataset (GSE35108) comparing normal and DCM induced pluripotent stem cell-derived cardiomyocytes.
- Performed differential gene expression analysis, functional enrichment, and protein-protein interaction network analysis.
Main Results:
- Identified 363 differentially expressed genes (DEGs) between normal and DCM samples.
- Enriched biological processes include blood vessel development, vasculature development, and cell adhesion.
- Key genes identified as potential biomarkers include MMP2, FLT1, CDH1, ITGB6, COL6A3, COL6A1, LAMC2, PENK, and APLNR.
Conclusions:
- Several genes, including MMP2, FLT1, and CDH1, show significant roles in DCM pathogenesis.
- These identified genes are implicated in critical pathways such as blood vessel development, cell adhesion, and ECM-receptor interactions.
- The identified genes represent promising candidates for novel biomarkers in DCM detection and management.
Abstract:
Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy that account for the majority of heart failure cases. The present study aimed to reveal the underlying molecular mechanisms of DCM and provide potential biomarkers for detection of this condition. The public dataset of GSE35108 was downloaded, and 4 normal induced pluripotent stem cell (iPSC)-derived cardiomyocytes (N samples) and 4 DCM iPSC-derived cardiomyocytes (DCM samples) were utilized. Raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between N and DCM samples. Crucial functions and pathway enrichment analysis of DEGs were investigated, and protein-protein interaction (PPI) network analysis was conducted. Furthermore, a module network was extracted from the PPI network, followed by enrichment analysis. A set of 363 DEGs were identified, including 253 upregulated and 110 downregulated genes. Several biological processes (BPs), such as blood vessel development and vasculature development (FLT1 and MMP2), cell adhesion (CDH1, ITGB6, COL6A3, COL6A1 and LAMC2) and extracellular matrix (ECM)-receptor interaction pathway (CDH1, ITGB6, COL6A3, COL6A1 and LAMC2), were significantly enriched by these DEGs. Among them, MMP2, CDH1 and FLT1 were hub nodes in the PPI network, while COL6A3, COL6A1, LAMC2 and ITGB6 were highlighted in module 3 network. In addition, PENK and APLNR were two crucial nodes in module 2, which were linked to each other. In conclusion, several potential biomarkers for DCM were identified, such as MMP2, FLT1, CDH1, ITGB6, COL6A3, COL6A1, LAMC2, PENK and APLNR. These genes may serve significant roles in DCM via involvement of various BPs, such as blood vessel and vasculature development and cell adhesion, and the ECM-receptor interaction pathway.
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