Research Paper Volume 15, Issue 12 pp 5497—5513

Integrative analysis of single-cell and bulk RNA sequencing unveils the senescence landscape in ischemic stroke

Longhui Fu1,2, *, , Beibei Yu1,2, *, , Yongfeng Zhang1,2, , Shuai Cao4, , Boqiang Lv1,2, , Yunze Tian1,2,3, , Huangtao Chen1,2, , Shijie Yang1,2, , Yutian Hu1,2, , Jinghua Hua1,2, , Pengyu Ren1,2, , Jianzhong Li1,3, , Shouping Gong1,2,5, ,

  • 1 Xi’an Jiaotong University, Xi’an, China
  • 2 Department of Neurosurgery, Second Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, China
  • 3 Department of Thoracic Surgery, Second Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, China
  • 4 Department of Orthopedics, Civil Aviation General Hospital, Chaoyang, Beijing, China
  • 5 Xi’an Medical University, Xi’an, China
* Co-first author

Received: April 6, 2023       Accepted: May 27, 2023       Published: June 28, 2023
How to Cite

Copyright: © 2023 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Ischemic stroke (IS) is a fatal neurological disease that occurs when the blood flow to the brain is disrupted, leading to brain tissue damage and functional impairment. Cellular senescence, a vital characteristic of aging, is associated with a poor prognosis for IS. This study explores the potential role of cellular senescence in the pathological process following IS by analyzing transcriptome data from multiple datasets (GSE163654, GSE16561, GSE119121, and GSE174574). By using bioinformatics methods, we identified hub-senescence-related genes such as ANGPTL4, CCL3, CCL7, CXCL16, and TNF and verified them using quantitative reverse transcription polymerase chain reaction. Further analysis of single-cell RNA sequencing data suggests that MG4 microglial is highly correlated with cellular senescence in MCAO, and might play a crucial role in the pathological process after IS. Additionally, we identified retinoic acid as a potential drug for improving the prognosis of IS. This comprehensive investigation of cellular senescence in various brain tissues and peripheral blood cell types provides valuable insights into the underlying mechanisms of the pathology of IS and identifies potential therapeutic targets for improving patient outcomes.


IS: ischemia stroke; SASP: senescence-associated secretory phenotype; scRNA-seq: single-cell RNA sequencing; HSRG: hub senescence-related gene; bulk RNA-seq: bulk RNA-sequencing; MCAO: middle cerebral artery occlusion; DEGs: differentially expressed genes; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; TTC: triphenyl tetrazolium chloride; RT-qPCR: reverse transcription polymerase chain reaction; ROC: receiver operating characteristic; DCA: decision curve analysis; UMAP: uniform manifold approximation and projection; SRGs: senescence-related genes; AUC: area under the curve; TFs: transcription factors.