Scholarlink

Background <p>Abnormal glycolytic metabolism plays a significant role in pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH), yet the specific mechanisms remain unclear. The primary objective of this study is to investigate the key regulatory mechanisms of glycolysis in IPAH.</p> Methods <p>Bulk and single-cell sequencing data obtained from IPAH patient tissue samples were downloaded from the GEO database. scMetabolism and AUCcell analyses of the IPAH single-cell sequencing data were carried out to quantify the glycolytic metabolic activity and identify the main cell types regulating glycolysis, respectively. The ssGSEA method was used to assess the glycolytic activity in each bulk sample within the bulk sequencing data. Differential analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network analysis were conducted to identify key genes associated with glycolysis in IPAH samples. Single-cell sequencing and a monocrotaline (MCT)-induced model of PH in rats were utilized to validate the expression of these key genes.</p> Results <p>Single-cell sequencing data indicated that IPAH patients displayed increased glycolytic activity, which was primarily regulated by fibroblasts. Similarly, bulk transcriptomic data revealed a significant increase in glycolytic activity in IPAH patients. Differential analysis, WGCNA, PPI network analysis, and integrated single-cell analysis further identified insulin-like growth factor-1 (IGF1), lysyl-tRNA synthetase (KARS), caspase-3 (CASP3), and cyclin-dependent kinase inhibitor 2&#xa0;A (CDKN2A) as key genes associated with fibroblast-mediated glycolysis in IPAH patients. Differential expression of IGF1, KARS, CASP3, and CDKN2A was also observed in our in vivo model of PH.</p> Conclusion <p>Our study identifies IGF1, KARS, CASP3, and CDKN2A as key regulatory genes in glycolysis in IPAH, which provides the basis for the development of targeted therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Combined analysis of single-cell and bulk transcriptome sequencing data identifies critical glycolysis genes in idiopathic pulmonary arterial hypertension

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月26日

查看全文
  • Xuan Gao,
  • Youli Fan,
  • Guijia Wang,
  • Jiangjiang Xu,
  • Runwei Deng,
  • Jiangwei Song,
  • Binfeng Sun,
  • Yongbing Wang,
  • Zixuan Wu,
  • Ruyi Jia,
  • Jing Huang,
  • Huiyu He,
  • Lei Gao,
  • Yihao Zhang,
  • Na Sun,
  • Bingxiang Wu

摘要

Background

Abnormal glycolytic metabolism plays a significant role in pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH), yet the specific mechanisms remain unclear. The primary objective of this study is to investigate the key regulatory mechanisms of glycolysis in IPAH.

Methods

Bulk and single-cell sequencing data obtained from IPAH patient tissue samples were downloaded from the GEO database. scMetabolism and AUCcell analyses of the IPAH single-cell sequencing data were carried out to quantify the glycolytic metabolic activity and identify the main cell types regulating glycolysis, respectively. The ssGSEA method was used to assess the glycolytic activity in each bulk sample within the bulk sequencing data. Differential analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network analysis were conducted to identify key genes associated with glycolysis in IPAH samples. Single-cell sequencing and a monocrotaline (MCT)-induced model of PH in rats were utilized to validate the expression of these key genes.

Results

Single-cell sequencing data indicated that IPAH patients displayed increased glycolytic activity, which was primarily regulated by fibroblasts. Similarly, bulk transcriptomic data revealed a significant increase in glycolytic activity in IPAH patients. Differential analysis, WGCNA, PPI network analysis, and integrated single-cell analysis further identified insulin-like growth factor-1 (IGF1), lysyl-tRNA synthetase (KARS), caspase-3 (CASP3), and cyclin-dependent kinase inhibitor 2 A (CDKN2A) as key genes associated with fibroblast-mediated glycolysis in IPAH patients. Differential expression of IGF1, KARS, CASP3, and CDKN2A was also observed in our in vivo model of PH.

Conclusion

Our study identifies IGF1, KARS, CASP3, and CDKN2A as key regulatory genes in glycolysis in IPAH, which provides the basis for the development of targeted therapies.