Scholarlink

Background <p>The rapid accumulation of lactate following cerebral ischemia has been well documented, however, the pathophysiological mechanisms underlying hyperlactate-induced lactylation in modulating neurological injury and prognosis of acute ischemic stroke (AIS) remain to be fully elucidated.</p> Methods <p>We constructed transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 60 AIS patients and 60 healthy controls using the Illumina sequencing platform. Unsupervised consensus clustering based on 56 lactylation-related genes (LRGs) was applied to stratify AIS molecular subtypes. Single-cell sequencing data analysis was conducted to evaluate the regulatory effects of LRGs enrichment on inter-neuronal communication.</p> Results <p>265 differentially expressed genes (DEGs), including 162 upregulated and 103 downregulated, were identified between AIS patients and healthy controls. And DEGs were found to be enriched in natural killer cell-mediated cytotoxicity, cytokine-cytokine receptor interaction, and TGF-β signaling pathways. Unsupervised consensus clustering stratified AIS into two subtypes, with AIS2 exhibiting more severe neuronal injury and inflammatory responses. Single-cell sequencing analysis revealed that LRGs were predominantly enriched in NK&amp;T cells following cerebral ischemia. Cell communication analysis further suggested that LRGs might regulate interactions between NK&amp;T cells and neural cells via the Nampt-Insr and Tnf-Tnfsf1b ligand-receptor pair. LASSO regression selected four prognosis-related genes (SUMO2, SUB1, LSP1, EEF1G) with robust diagnostic efficacy for prognosis prediction (AUC value = 0.805, sensitivity = 0.875, specificity = 0.706).</p> Conclusion <p>Our findings reveal significant correlations between LRGs in AIS patients and both neurological deficit severity and inflammatory status, highlighting LRGs as potential prognostic biomarkers for AIS.</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

Lactylation-related genes contribute to neurological injury and prognosis of acute ischemic stroke based on transcriptome and single-cell sequencing analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月22日

查看全文
  • Jie Li,
  • Lulu Zhu,
  • Xiaolan Huang,
  • Miaomiao Xu,
  • Yun Liang,
  • Jing Zeng,
  • Zihan Song,
  • Lian Gu,
  • Jialei Yang,
  • Li Su

摘要

Background

The rapid accumulation of lactate following cerebral ischemia has been well documented, however, the pathophysiological mechanisms underlying hyperlactate-induced lactylation in modulating neurological injury and prognosis of acute ischemic stroke (AIS) remain to be fully elucidated.

Methods

We constructed transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 60 AIS patients and 60 healthy controls using the Illumina sequencing platform. Unsupervised consensus clustering based on 56 lactylation-related genes (LRGs) was applied to stratify AIS molecular subtypes. Single-cell sequencing data analysis was conducted to evaluate the regulatory effects of LRGs enrichment on inter-neuronal communication.

Results

265 differentially expressed genes (DEGs), including 162 upregulated and 103 downregulated, were identified between AIS patients and healthy controls. And DEGs were found to be enriched in natural killer cell-mediated cytotoxicity, cytokine-cytokine receptor interaction, and TGF-β signaling pathways. Unsupervised consensus clustering stratified AIS into two subtypes, with AIS2 exhibiting more severe neuronal injury and inflammatory responses. Single-cell sequencing analysis revealed that LRGs were predominantly enriched in NK&T cells following cerebral ischemia. Cell communication analysis further suggested that LRGs might regulate interactions between NK&T cells and neural cells via the Nampt-Insr and Tnf-Tnfsf1b ligand-receptor pair. LASSO regression selected four prognosis-related genes (SUMO2, SUB1, LSP1, EEF1G) with robust diagnostic efficacy for prognosis prediction (AUC value = 0.805, sensitivity = 0.875, specificity = 0.706).

Conclusion

Our findings reveal significant correlations between LRGs in AIS patients and both neurological deficit severity and inflammatory status, highlighting LRGs as potential prognostic biomarkers for AIS.