中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3209-3224.doi: 10.4103/NRR.NRR-D-24-01669

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

缺血性脑卒中单核细胞特征：多尺度转录组学解码

  

  • 出版日期:2026-07-15 发布日期:2026-03-31
  • 基金资助:
    国家自然科学基金项目（82471361）、湖南省自然科学基金-优秀青年科学基金（2021JJ20095）、湖南省重点研发计划（2020SK2063）、中南大学教育教学改革研究项目（2021jy145）、湖南省自然科学基金面上项目（2020JJ4134）、中南大学研究生自主探索创新项目（2023ZZTS0595）

Decoding monocyte signatures in ischemic stroke: A multi-scale transcriptomic approach

Yanyi Peng1, Bo Xiao1, 2, Mengqi Zhang1, 2, *   

  1. 1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China;  2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Online:2026-07-15 Published:2026-03-31
  • Contact: Mengqi Zhang, MD, PhD, zhangmengqi8912@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82471361 (to MZ); the Natural Science Foundation for Excellent Young Scholars of Hunan Province, No. 2021JJ20095 (to MZ); the Key Research and Development Program of Hunan Province, No. 2020SK2063 (to MZ); the Research Project on Education and Teaching Innovation of Central South University, No. 2021jy145 (to MZ); the Natural Science Foundations of Hunan Province, No. 2020JJ4134 (to MZ); the Fundamental Research Funds for the Central Universities of Central South University, No. 2023ZZTS0595 (to YP).

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摘要：

单核细胞在脑卒中后免疫浸润中起着至关重要的作用；然而，单核细胞在缺血性脑卒中中协调的复杂免疫调节网络仍不明确。实验采用了一种结合单细胞和批量转录组学的多组学方法。CellChat 分析揭示了细胞间的通讯网络。通过 Lasso 回归确定了关键基因，并建立了预测模型。利用 ssGSEA 对免疫细胞浸润动态进行了量化。GSEA 和 GSVA 分析了核心基因的疾病调控通路。利用mircode和RcisTarget研究了MicroRNAs网络和转录因子。实验进一步采用氧糖剥夺和大脑中动脉阻塞模型进行验证，重点研究 Abhd2 对单核细胞功能的影响。结果发现，大脑中动脉阻塞脑组织样本中单核细胞含量明显升高，并确定了与免疫炎症、趋化因子信号转导和细胞受体功能相关的关键单核细胞基因。实验鉴定了 7 个单核细胞关键基因（SERPINH1，TCF4，ABHD2，PLAC8，GNGT2，CDH5，SLC22A8），并构建高精度预测模型。CD274 与这 7 个基因密切相关，表明这是一个潜在的免疫调节轴。体内脑缺血模型验证外周单核细胞关键基因显著差异；体外氧糖剥夺实验发现 Abhd2 过表达可促进单核细胞增殖与吞噬、降低活性氧生成。总之，实验绘制了脑卒中后单核细胞通讯网络图，确定了关键信号通路，阐明了调控机制，并验证了关键基因（尤其是 Abhd2）的功能重要性。这些发现为开发针对缺血性脑卒中的免疫调节疗法和精准诊断奠定了基础。


https://orcid.org/0000-0003-2090-6320 (Mengqi Zhang)

关键词: ABHD2, 大量RNA测序, 细胞聊天, 诊断模型, 基因特征, 缺血性脑卒中, 单核细胞, 吞噬作用, 活性氧, 单细胞转录组学

Abstract: Monocytes play a crucial role in post-stroke immune infiltration, yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood. This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke. Here, we used a multi-omics approach combining single-cell and bulk transcriptomics. CellChat analysis revealed intercellular communication networks, while key genes were identified and predictive models built through Lasso regression. Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis. Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes. MicroRNA networks and transcription factors were investigated using mircode and RcisTarget. Experimental validation was performed using oxygen–glucose deprivation and transient middle cerebral artery occlusion models, focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function. We observed significantly elevated monocyte content in stroke brain tissue samples, and identified key monocyte genes associated with immune inflammation, chemokine signaling, and cell receptor function. A robust seven-gene predictive model for ischemic stroke was developed. CD274 strongly correlated with these seven genes, suggesting a potential immunomodulatory axis. In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes. In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen–glucose deprivation while reducing reactive oxygen species generation. In conclusion, this study maps post-stroke monocyte communication networks, identifies key signaling pathways, identifies regulatory mechanisms, and validates the functional importance of key genes, particularly abhydrolase domain-containing protein 2. These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.

Key words: abhydrolase domain-containing protein 2, bulk-RNA sequencing, CellChat, diagnosis model, gene signature, ischemic stroke, monocytes, phagocytosis, reactive oxygen species, single-cell transcriptomics