• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

生物信息学分析鉴定载脂蛋白 E 为调控脊髓损伤后巨噬细胞和小胶质细胞神经炎症的枢纽基因。

Bioinformatics analysis identified apolipoprotein E as a hub gene regulating neuroinflammation in macrophages and microglia following spinal cord injury.

机构信息

Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Department of Comprehensive Medical Treatment Ward, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Front Immunol. 2022 Aug 24;13:964138. doi: 10.3389/fimmu.2022.964138. eCollection 2022.

DOI:10.3389/fimmu.2022.964138
PMID:36091018
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9448857/
Abstract

Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations , but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI.

摘要

巨噬细胞和小胶质细胞在脊髓损伤 (SCI) 后的慢性神经炎症中发挥重要作用。尽管巨噬细胞和小胶质细胞具有相似的功能，但它们的吞噬和稳态能力不同。很难区分这两种细胞群，但单细胞分析可以提高我们对它们的身份和异质性的理解。我们对单细胞 RNA 测序数据集 GSE159638 进行了生物信息学分析，发现载脂蛋白 E (APOE) 是 SCI 亚急性期和慢性期巨噬细胞和小胶质细胞中的一个枢纽基因。然后，我们在小鼠颈段脊髓半切模型中验证了这些转录组变化，并观察到 SCI 后巨噬细胞和小胶质细胞中髓鞘摄取、脂质滴和溶酶体积累增加。最后，我们观察到敲除 APOE 加重了神经功能障碍，增加了神经炎症，并加剧了白质的丢失。靶向 APOE 和相关的胆固醇外排代表了一种有前途的策略，可以减少 SCI 后的神经炎症并促进恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/f6c4998151e7/fimmu-13-964138-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/090080d426ea/fimmu-13-964138-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/2e383944bf14/fimmu-13-964138-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/556a9a1af76f/fimmu-13-964138-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/3c0e58e95b65/fimmu-13-964138-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/00df9ecbd572/fimmu-13-964138-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/048fb3c00425/fimmu-13-964138-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/0d0f790200c2/fimmu-13-964138-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/f6c4998151e7/fimmu-13-964138-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/090080d426ea/fimmu-13-964138-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/2e383944bf14/fimmu-13-964138-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/556a9a1af76f/fimmu-13-964138-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/3c0e58e95b65/fimmu-13-964138-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/00df9ecbd572/fimmu-13-964138-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/048fb3c00425/fimmu-13-964138-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/0d0f790200c2/fimmu-13-964138-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da48/9448857/f6c4998151e7/fimmu-13-964138-g008.jpg

相似文献

1
Bioinformatics analysis identified apolipoprotein E as a hub gene regulating neuroinflammation in macrophages and microglia following spinal cord injury.生物信息学分析鉴定载脂蛋白 E 为调控脊髓损伤后巨噬细胞和小胶质细胞神经炎症的枢纽基因。
Front Immunol. 2022 Aug 24;13:964138. doi: 10.3389/fimmu.2022.964138. eCollection 2022.
2
Impairment of autophagy after spinal cord injury potentiates neuroinflammation and motor function deficit in mice.脊髓损伤后自噬的损伤会加剧小鼠的神经炎症和运动功能缺陷。
Theranostics. 2022 Jul 11;12(12):5364-5388. doi: 10.7150/thno.72713. eCollection 2022.
3
Proteomics and bioinformatics reveal insights into neuroinflammation in the acute to subacute phases in rat models of spinal cord contusion injury.蛋白质组学和生物信息学揭示了急性至亚急性期大鼠脊髓挫伤模型中神经炎症的见解。
FASEB J. 2021 Jul;35(7):e21735. doi: 10.1096/fj.202100081RR.
4
Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.载脂蛋白E作为创伤性脊髓损伤后新型治疗性神经保护靶点。
Exp Neurol. 2018 Jan;299(Pt A):97-108. doi: 10.1016/j.expneurol.2017.10.014. Epub 2017 Oct 19.
5
Combination of single-cell and bulk RNA seq reveals the immune infiltration landscape and targeted therapeutic drugs in spinal cord injury.单细胞和批量 RNA 测序的组合揭示了脊髓损伤中的免疫浸润景观和靶向治疗药物。
Front Immunol. 2023 Jan 19;14:1068359. doi: 10.3389/fimmu.2023.1068359. eCollection 2023.
6
miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1.miR-223 通过上调 ABCA1 加速脊髓损伤后小胶质细胞中脂滴的清除。
J Transl Med. 2024 Jul 15;22(1):659. doi: 10.1186/s12967-024-05480-5.
7
Lentivirus-mediated downregulation of α-synuclein reduces neuroinflammation and promotes functional recovery in rats with spinal cord injury.慢病毒介导的α-突触核蛋白下调减轻大鼠脊髓损伤后的神经炎症并促进功能恢复。
J Neuroinflammation. 2019 Dec 30;16(1):283. doi: 10.1186/s12974-019-1658-2.
8
Programmed death protein 1 is essential for maintaining the anti-inflammatory function of infiltrating regulatory T cells in a murine spinal cord injury model.程序性死亡蛋白 1 对于维持浸润调节性 T 细胞在小鼠脊髓损伤模型中的抗炎功能是必需的。
J Neuroimmunol. 2021 May 15;354:577546. doi: 10.1016/j.jneuroim.2021.577546. Epub 2021 Mar 17.
9
Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris.脊髓损伤中的巨噬细胞：从接触髓磷脂碎片后的表型和功能变化
Glia. 2015 Apr;63(4):635-51. doi: 10.1002/glia.22774. Epub 2014 Nov 28.
10
An Agonist of the Protective Factor SIRT1 Improves Functional Recovery and Promotes Neuronal Survival by Attenuating Inflammation after Spinal Cord Injury.保护性因子SIRT1的激动剂通过减轻脊髓损伤后的炎症反应来改善功能恢复并促进神经元存活。
J Neurosci. 2017 Mar 15;37(11):2916-2930. doi: 10.1523/JNEUROSCI.3046-16.2017. Epub 2017 Feb 13.

引用本文的文献

1
Lipid-Laden Microglia: Characterization and Roles in Diseases.脂质负载的小胶质细胞：疾病中的特征与作用
Cells. 2025 Aug 19;14(16):1281. doi: 10.3390/cells14161281.
2
Generation and clearance of myelin debris after spinal cord injury.脊髓损伤后髓磷脂碎片的产生与清除
Neural Regen Res. 2026 Apr 1;21(4):1512-1527. doi: 10.4103/NRR.NRR-D-24-01405. Epub 2025 Apr 29.
3
The role of foam cells in spinal cord injury: challenges and opportunities for intervention.泡沫细胞在脊髓损伤中的作用：干预的挑战与机遇。

本文引用的文献

1
Time-resolved single-cell RNAseq profiling identifies a novel subpopulation of inflammatory myeloid cells with delayed cytotoxic profile in chronic spinal cord injury.时间分辨单细胞RNA测序分析鉴定出慢性脊髓损伤中具有延迟细胞毒性特征的新型炎性髓样细胞亚群。
Heliyon. 2023 Aug 6;9(8):e18339. doi: 10.1016/j.heliyon.2023.e18339. eCollection 2023 Aug.
2
Myelin and non-myelin debris contribute to foamy macrophage formation after spinal cord injury.髓磷脂和非髓磷脂碎片在后脊髓损伤中导致泡沫状巨噬细胞的形成。
Neurobiol Dis. 2022 Feb;163:105608. doi: 10.1016/j.nbd.2021.105608. Epub 2021 Dec 31.
3
Anatomical and behavioral outcomes following a graded hemi-contusive cervical spinal cord injury model in mice.
Front Immunol. 2024 Mar 13;15:1368203. doi: 10.3389/fimmu.2024.1368203. eCollection 2024.
4
Spinal apolipoprotein E is involved in inflammatory pain via regulating lipid metabolism and glial activation in the spinal dorsal horn.脊髓载脂蛋白 E 通过调节脊髓背角的脂质代谢和神经胶质细胞激活参与炎性疼痛。
Biol Direct. 2023 Dec 9;18(1):85. doi: 10.1186/s13062-023-00444-z.
5
Integrated Analysis of Immune Infiltration and Hub Pyroptosis-Related Genes for Multiple Sclerosis.多发性硬化症免疫浸润与关键焦亡相关基因的综合分析
J Inflamm Res. 2023 Sep 13;16:4043-4059. doi: 10.2147/JIR.S422189. eCollection 2023.
6
Curcumin-activated Olfactory Ensheathing Cells Improve Functional Recovery After Spinal Cord Injury by Modulating Microglia Polarization Through APOE/TREM2/NF-κB Signaling Pathway.姜黄素激活嗅鞘细胞通过 APOE/TREM2/NF-κB 信号通路调节小胶质细胞极化改善脊髓损伤后的功能恢复。
J Neuroimmune Pharmacol. 2023 Sep;18(3):476-494. doi: 10.1007/s11481-023-10081-y. Epub 2023 Sep 2.
7
Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after Spinal Cord Injury.未解决的髓磷脂源性胆固醇过度积累促成脊髓损伤后的瘢痕形成。
Research (Wash D C). 2023 May 4;6:0135. doi: 10.34133/research.0135. eCollection 2023.
在小鼠中进行分级半挫伤性颈脊髓损伤模型后的解剖学和行为学结果。
Behav Brain Res. 2022 Feb 15;419:113698. doi: 10.1016/j.bbr.2021.113698. Epub 2021 Nov 29.
4
clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.clusterProfiler 4.0：用于解释组学数据的通用富集工具。
Innovation (Camb). 2021 Jul 1;2(3):100141. doi: 10.1016/j.xinn.2021.100141. eCollection 2021 Aug 28.
5
Spinal Cord Injury Induces Permanent Reprogramming of Microglia into a Disease-Associated State Which Contributes to Functional Recovery.脊髓损伤诱导小胶质细胞永久性重编程为疾病相关状态，这有助于功能恢复。
J Neurosci. 2021 Oct 6;41(40):8441-8459. doi: 10.1523/JNEUROSCI.0860-21.2021. Epub 2021 Aug 20.
6
Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer's disease.斑块相关的人类小胶质细胞在阿尔茨海默病的嵌合模型中积累脂滴。
Mol Neurodegener. 2021 Jul 23;16(1):50. doi: 10.1186/s13024-021-00473-0.
7
Macrophage phagocytosis after spinal cord injury: when friends become foes.脊髓损伤后的巨噬细胞吞噬作用：当朋友变成敌人。
Brain. 2021 Nov 29;144(10):2933-2945. doi: 10.1093/brain/awab250.
8
Proteomics and bioinformatics reveal insights into neuroinflammation in the acute to subacute phases in rat models of spinal cord contusion injury.蛋白质组学和生物信息学揭示了急性至亚急性期大鼠脊髓挫伤模型中神经炎症的见解。
FASEB J. 2021 Jul;35(7):e21735. doi: 10.1096/fj.202100081RR.
9
Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord.单细胞分析损伤小鼠脊髓中的细胞异质性和相互作用。
J Exp Med. 2021 Aug 2;218(8). doi: 10.1084/jem.20210040. Epub 2021 Jun 16.
10
Galectin-3: a key player in microglia-mediated neuroinflammation and Alzheimer's disease.半乳糖凝集素-3：小胶质细胞介导的神经炎症和阿尔茨海默病中的关键因子。
Cell Biosci. 2021 Apr 27;11(1):78. doi: 10.1186/s13578-021-00592-7.