Scholarlink

<p>Ischemic stroke (IS) remains a leading cause of death and disability, with limited effective treatments in the acute phase. Mitophagy, the selective degradation of damaged mitochondria, plays a crucial role in cellular homeostasis and survival during IS. However, its exact mechanisms in stroke pathophysiology remain unclear. This study utilized a multi-omics approach, integrating gene expression data from bulk and single-cell RNA sequencing, to investigate the role of mitophagy-related genes (MRGs) in IS. We identified differentially expressed MRGs (DE-MRGs) in IS using bioinformatics techniques, including weighted gene co-expression network analysis (WGCNA) and machine learning models, which led to the identification of five core biomarkers: SRPRB, ATP5J, LSM7, DEGS1, and TGDS. Validation via qPCR and analysis of immune cell infiltration further supported their relevance. Single-cell analysis revealed significant differences in mitophagy activity in microglial subpopulations, with ATP5J showing dynamic expression patterns linked to stroke-induced mitochondrial dysfunction. Additionally, pseudo-time analysis suggested a progressive shift from homeostatic to disease-associated microglial states. Our findings highlight the complexity of mitophagy regulation in IS and suggest that targeting mitophagy-related pathways, such as ATP5J, could provide novel therapeutic strategies for IS management.</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

Single-cell and multi-omics analysis identifies mitophagy-related biomarkers and therapeutic targets in ischemic stroke

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月6日

查看全文
  • Zhan Cao,
  • Yingluan Wang,
  • Mingjian Sun,
  • Runyi Du,
  • Xu Feng,
  • Lin Wang,
  • Ziyi Zhao,
  • Wei Sun

摘要

Ischemic stroke (IS) remains a leading cause of death and disability, with limited effective treatments in the acute phase. Mitophagy, the selective degradation of damaged mitochondria, plays a crucial role in cellular homeostasis and survival during IS. However, its exact mechanisms in stroke pathophysiology remain unclear. This study utilized a multi-omics approach, integrating gene expression data from bulk and single-cell RNA sequencing, to investigate the role of mitophagy-related genes (MRGs) in IS. We identified differentially expressed MRGs (DE-MRGs) in IS using bioinformatics techniques, including weighted gene co-expression network analysis (WGCNA) and machine learning models, which led to the identification of five core biomarkers: SRPRB, ATP5J, LSM7, DEGS1, and TGDS. Validation via qPCR and analysis of immune cell infiltration further supported their relevance. Single-cell analysis revealed significant differences in mitophagy activity in microglial subpopulations, with ATP5J showing dynamic expression patterns linked to stroke-induced mitochondrial dysfunction. Additionally, pseudo-time analysis suggested a progressive shift from homeostatic to disease-associated microglial states. Our findings highlight the complexity of mitophagy regulation in IS and suggest that targeting mitophagy-related pathways, such as ATP5J, could provide novel therapeutic strategies for IS management.