Related Experiment Video
Updated: Jul 21, 2025
An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level
Published on: November 2, 2020
Identification of TGF-β-related genes in cardiac hypertrophy and heart failure based on single cell RNA sequencing
Kai Huang1, Hao Wu1, Xiangyang Xu1
1Department of Cardiovascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Insights
This study identifies six key TGF-β-related genes (TRGs) linked to cardiac hypertrophy and heart failure (HF). These genes, including ADAMTS2, show potential as novel therapeutic targets for HF treatment.
Area of Science:
- Cardiology
- Molecular Biology
- Genomics
Background:
- Heart failure (HF) is a global health burden, with pathological cardiac hypertrophy as a key phenotype.
- The transforming growth factor-beta (TGF-β) pathway has a complex role in HF, making TGF-β-related genes (TRGs) potential therapeutic targets.
- The specific roles of TRGs in HF at the single-cell level require further elucidation.
Purpose of the Study:
- To investigate the expression patterns and roles of TRGs during cardiac hypertrophy and HF progression.
- To identify potential therapeutic targets for cardiac hypertrophy and HF by analyzing TRGs at the single-cell level.
Main Methods:
- Integrated analysis of multiple single-cell RNA sequencing and transcriptome datasets for HF and hypertrophic cardiomyopathy.
- Employed Weighted Gene Co-expression Network Analysis (WGCNA), functional enrichment, and machine learning to identify hub genes.
- Validated key findings using a transverse aortic constriction mouse model and in vitro cell-based assays.
Main Results:
- High TGF-β activity was observed in cardiac fibroblasts and endothelial cells during HF progression.
- Six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) exhibited anomalous trends in cardiac hypertrophy.
- The TGF-β-MYC-ADAMTS2 axis was confirmed to regulate cardiac fibroblast activation in vitro.
Conclusions:
- Identified six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) through integrated omics data analysis.
- These six hub genes represent promising therapeutic targets for treating cardiac hypertrophy and HF.
Background:
Heart failure (HF) remains a huge medical burden worldwide. Pathological cardiac hypertrophy is one of the most significant phenotypes of HF. Several studies have reported that the TGF-β pathway plays a double-sided role in HF. Therefore, TGF-β-related genes (TRGs) may be potential therapeutic targets for cardiac hypertrophy and HF. However, the roles of TRGs in HF at the single-cell level remain unclear.
Method:
In this study, to analyze the expression pattern of TRGs during the progress of cardiac hypertrophy and HF, we used three public single-cell RNA sequencing datasets for HF (GSE161470, GSE145154, and GSE161153), one HF transcriptome data (GSE57338), and one hypertrophic cardiomyopathy transcriptome data (GSE141910). Weighted gene co-expression network analysis (WGCNA), functional enrichment analysis and machine learning algorithms were used to filter hub genes. Transverse aortic constriction mice model, CCK-8, wound healing assay, quantitative real-time PCR and western blotting were used to validate bioinformatics results.
Results:
We observed that cardiac fibroblasts (CFs) and endothelial cells showed high TGF-β activity during the progress of HF. Three modules (royalblue, brown4, and darkturquoize) were identified to be significantly associated with TRGs in HF. Six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) showed anomaly trend in cardiac hypertrophy. We further validated the regulation of the TGF-β-MYC-ADAMTS2 axis on CFs activation in vitro.
Conclusions:
This study identified six hub genes (TANC2, ADAMTS2, DYNLL1, MRC2, EGR1, and OTUD1) by integrating scRNA and transcriptome data. These six hub genes might be therapeutic targets for cardiac hypertrophy and HF.
