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中华细胞与干细胞杂志(电子版) ›› 2026, Vol. 16 ›› Issue (04) : 227 -232. doi: 10.3877/cma.j.issn.2095-1221.2026.04.005

论著

基于转录组测序和单细胞RNA测序探讨脑出血后神经损伤修复的关键基因和细胞通讯
宋海涛1,2, 宋仁兴1,3,(), 赵千云1, 聂文2, 陈森2, 宋德文2, 潘峰2, 赵波2   
  1. 1261000 潍坊,山东第二医科大学临床医学院
    2266300 青岛,同济大学附属东方医院胶州医院神经外科
    3261000 潍坊,山东省潍坊市人民医院神经外科
  • 收稿日期:2025-08-18 出版日期:2026-08-01
  • 通信作者: 宋仁兴

Exploring the key genes and cell communication in neural injury repair after intracerebral hemorrhage based on transcriptome sequencing and single-cell RNA sequencing

Haitao Song1,2, Renxing Song1,3,(), Qianyun Zhao1, Wen Nie2, Sen Chen2, Dewen Song2, Feng Pan2, Bo Zhao2   

  1. 1School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, China
    2Department of Neurosurgery, Jiaozhou Hospital, Dongfang Hospital Affiliated to Tongji University, Qingdao 266300, China
    3Department of Neurosurgery, Weifang People's Hospital, Weifang 261000, China
  • Received:2025-08-18 Published:2026-08-01
  • Corresponding author: Renxing Song
引用本文:

宋海涛, 宋仁兴, 赵千云, 聂文, 陈森, 宋德文, 潘峰, 赵波. 基于转录组测序和单细胞RNA测序探讨脑出血后神经损伤修复的关键基因和细胞通讯[J/OL]. 中华细胞与干细胞杂志(电子版), 2026, 16(04): 227-232.

Haitao Song, Renxing Song, Qianyun Zhao, Wen Nie, Sen Chen, Dewen Song, Feng Pan, Bo Zhao. Exploring the key genes and cell communication in neural injury repair after intracerebral hemorrhage based on transcriptome sequencing and single-cell RNA sequencing[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2026, 16(04): 227-232.

目的

探讨脑出血后神经损伤修复的关键基因、核心细胞亚群及细胞通讯机制。

方法

从GEO数据库下载大鼠脑出血转录组数据集GSE288102、小鼠脑出血小胶质细胞转录组数据集GSE266602及小鼠脑出血脑组织单细胞RNA测序数据集GSE167593。采用limma包筛选差异表达基因(DEGs),取两组转录组交集获得共同DEGs;通过DAVID进行GO/KEGG富集分析,STRING构建蛋白互作网络,Cytoscape筛选核心基因;利用Seurat完成单细胞质控、降维、聚类与细胞注释;采用CellChat解析细胞间通讯通路。

结果

共筛选出96个共同DEGs;GO富集主要集中于免疫细胞活化、白细胞活化及损伤修复相关过程,KEGG富集于ECM受体通路与PI3K-Akt信号通路。筛选出LGALS3、ITGB2、TLR2、TIMP1、FN1、CD44、ICAM1、CCL2、TGFB1、ITGAM共10个关键基因。单细胞RNA分析鉴定出神经元、少突胶质细胞、少突胶质前体细胞、小胶质细胞、星形胶质细胞5类核心细胞群;关键基因在各细胞群呈特异性表达:神经元中LGALS3下调、TGFB1上调;星形胶质细胞中TGFB1、CCL2、ICAM1等上调;小胶质细胞中FN1、TGFB1上调。细胞通讯显示,SPP1- (ITGA5+ITGB1)与SPP1- (ITGAV+ ITGB1)是脑出血后神经修复的核心信号通路。

结论

本研究明确了脑出血后神经损伤修复10个关键基因、5类关键细胞群及2条核心细胞通讯通路,为脑出血后神经修复机制研究与潜在靶点筛选提供了可靠依据。

Objective

To explore the key genes, core cell subsets, and cell communication mechanisms underlying neural injury repair after intracerebral hemorrhage.

Methods

The rat intracerebral hemorrhage transcriptome dataset GSE288102, mouse intracerebral hemorrhage microglia transcriptome dataset GSE266602, and mouse intracerebral hemorrhage brain tissue single-cell RNA sequencing dataset GSE167593 were downloaded from the GEO database. The limma package was used to screen differentially expressed genes (DEGs), and the intersection of DEGs from the two transcriptome datasets was obtained to identify common DEGs. GO and KEGG enrichment analyses were performed using the DAVID database, and a protein-protein interaction (PPI) network was constructed via the STRING database. Key genes were screened using Cytoscape. Quality control, dimensionality reduction, clustering, and cell annotation of single-cell data were completed with the Seurat package, and intercellular communication pathways were analyzed using CellChat.

Results

A total of 96 common DEGs were identified. GO terms was mainly enriched in immune cell activation, leukocyte activation, and injury repair-related processes, while KEGG enrichment was found in the ECM-receptor interaction pathway and the PI3K-Akt signaling pathway. Ten hub genes were screened, including LGALS3, ITGB2, TLR2, TIMP1, FN1, CD44, ICAM1, CCL2, TGFB1, and ITGAM. Single-cell RNA analysis identified five core cell populations: neurons, oligodendrocytes, oligodendrocyte precursor cells, microglia, and astrocytes. The hub genes showed specific expression in each cell subset: LGALS3 was downregulated and TGFB1 was upregulated in neurons; TGFB1, CCL2, and ICAM1 were significantly upregulated in astrocytes; and FN1 and TGFB1 were upregulated in microglia. Cell communication analysis revealed that SPP1- (ITGA5+ITGB1) and SPP1- (ITGAV+ITGB1) were the core signaling pathways for neural repair after intracerebral hemorrhage.

Conclusion

This study identified 10 core genes, 5 key cell populations, and 2 core cell communication pathways involved in neural injury repair after intracerebral hemorrhage, providing a reliable basis for investigating the mechanisms of neural repair and screening potential therapeutic targets for intracerebral hemorrhage.

图1 研究流程
图2 GSE288102和GSE266602数据集中对照组和脑出血组基因表达差异分析
图3 GO和KEGG功能富集图
图4 蛋白相互作用网络关键核心基因
图5 脑损伤后神经损伤单细胞测序细胞亚群分析
图6 10个核心基因在细胞亚群中的分布情况
图7 SPP1信号通路中细胞相互作用分析注:线粗度与作用强度呈正比,分别为SPP1、TGEb、CCL、TCALECTIN信号通路中细胞细胞相互作用
1
Wolsink JCliteur MPvan Asch CJJ,et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage, according to age, sex, and country income level: a systematic review and meta-analysis[J]. Lancet Reg Health Eur, 2024, 49:101180.
2
Fedder BA, Sander NH, MacLaren M, et al. Motor rehabilitation provides modest functional benefits after intracerebral hemorrhage: A systematic review and meta-analysis of translational rehabilitation studies[J]. Transl Stroke Res, 2025, 16(2):484-511.
3
Xiang R, Wang J, Chen Z, et al. Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution[J]. Neuron, 2025, 113(13):2102-2122.e7.
4
任廷婷, 王宇红, 唐璎娟, 等. 基于HDAC5/MEF2C通路探讨柴金解郁安神方调节失眠并发抑郁大鼠海马神经元突触可塑性的机制[J]. 中国药理学通报, 2024, 40(7):1248-1257.
5
Au NPB, Wu T, Chen, et al. Genome-wide study reveals novel roles for formin-2 in axon regeneration as a microtubule dynamics regulator and therapeutic target for nerve repair[J]. Neuron, 2023, 111(24):3970-3987.e8.
6
Han J, Zhang J, Yao X, et al. Mechanism of HDAC1 regulating iron overload-induced neuronal oxidative damage after cerebral hemorrhage[J].Mol Neurobiol, 2024, 61(10):7549-7566.
7
Ijabi R, Kaminsky ZA, Roozehdar P, et al. Role of S100 and YKL40 on intraventricular cerebral hemorrhages in the preterm infant and the neuroprotective role of miR-138- siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 in neonatal mice with nerve injury[J]. Curr Med Chem, 2024, 31(34):5638-5656.
8
Shen J, Wang J, Zhou S, et al. Integrating bioinformatics and machine learning to unravel shared mechanisms and biomarkers in chronic obstructive pulmonary disease and type 2 diabetes[J]. Postgrad Med J, 2024, 101(1196):535-544.
9
马晓维, 周喜燕, 李彬, 等. mir-325-3p激活RIPK3/TFEB信号通路减轻脑出血大鼠神经元损伤[J]. 中国临床解剖学杂志, 2023, 41(4):422-427.
10
Li Y, Qiao Y, Li H, et al. Mechanism of the mongolian medicine eerdun wurile basic formula in improving postoperative cognitive dysfunction by inhibiting apoptosis through the SIRT1/p53 signaling pathway[J]. J Ethnopharmacol, 2023, 309:116312.
11
余剑媛, 周惠芬, 郭建文, 等. 基于生物信息学探讨中风醒脑液对脑出血后神经系统及免疫系统的影响[J]. 中药新药与临床药理, 2024, 35(4):451-458.
12
中国卒中学会. 中国脑出血诊治指南(2024)[J]. 中华神经科杂志, 2024, 57(9):665-684.
13
周惠芬, 郭建文, 余剑媛, 等. 脑出血后神经免疫炎症与损伤修复的生物信息学分析[J]. 中国中药杂志, 2024, 49(8):2312-2319.
14
Hu L, Chen Z, Liu J, et al. Extracellular vesicles from bone marrow-derived macrophages enriched in ARG1 enhance microglial phagocytosis and haematoma clearance following intracerebral haemorrhage[J]. J Extracell Vesicles, 2025, 14(1):e70041.
15
Xiang R, Wang J, Chen Z, et al. Spatiotemporal transcriptomic maps of mouse intracerebral hemorrhage at single-cell resolution[J]. Neuron, 2025, 113(13):2102-2122.
16
Wu Z, Chen D, Chen S, et al. snRNA-seq reveals key transcription factors in the inflammatory response of microglia after intracerebral hemorrhage[J]. Sci Rep, 2025, 15(1):40961.
17
安岩, 朱祥, 王博, 等. 单细胞测序分析脊髓损伤修复的关键基因和细胞通讯[J]. 中华骨科杂志, 2025, 45(5):302-309.
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