仅在永久性脑缺血后短暂出现的星形胶质细胞样NG2胶质细胞亚群  

Transient Astrocyte-like NG2 Glia Subpopulation Emerges Solely following Permanent Brain Ischemia

作　　者：Denisa Kirdajova Lukas Valihrach Martin Valny Jan Kriska Daniela Krocianova Sarka Benesova Pavel Abaffy Daniel Zucha Ruslan Klassen Denisa Kolenicova Pavel Honsa Mikael Kubista Miroslava Anderova 杜一星(编译) 

机构地区：[1]Department of Cellular Neurophysiology,Institute of Experimental Medicine,Czech Academy of Sciences,Prague,Czech Republic [2]Second Faculty of Medicine,Charles University,Czech Republic [3]Laboratory of Gene Expression,Institute of Biotechnology CAS,BIOCEV,Vestec,Czech Republic [4]Faculty of Chemical Technology,Laboratory of Informatics and Chemistry,University of Chemistry and Technology,Prague,Czech Republic [5]Faculty of Science,Charles University,Prague,Czech Republic [6]不详

出　　处：《神经损伤与功能重建》2021年第8期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：NG2神经胶质细胞在生理和病理条件下显示出较强的增殖和分化潜力。本研究用3月龄Cspg4启动子下由tdTomato标记NG2神经胶质细胞的小鼠,在不同类型的脑疾病模型(局灶性脑缺血、皮质刺伤和脱髓鞘)中研究NG2细胞的增殖和分化潜力,研究首先采用单细胞RT-qPCR和Kohonen自组织映射图分析从未损伤和特定损伤后的皮质/胼胝体分离的tdTomato阳性细胞,比较不同损伤后NG2神经胶质细胞表达概况。这种方法使我们能够区分NG2神经胶质细胞和少突胶质细胞,每个细胞群都包含4个不同的亚群。基因表达谱显示,表达GFAP(反应性星形胶质细胞的标志物)的NG2胶质细胞亚群仅在局灶性脑缺血后短暂出现。然而,在较轻的损伤后(皮质刺伤和脱髓鞘),反映少突胶质细胞成熟不同阶段的亚群明显占优势。免疫组织化学也证实了不同亚群的损伤依赖性发生率。本研究使用单细胞RNA测序分析这种独特的短暂星形胶质细胞样NG2胶质细胞亚群,并采用膜片钳技术揭示了其基本的细胞膜特性。综上所述,我们证明了星形胶质细胞样NG2神经胶质细胞是仅在局灶性脑缺血后短暂出现的NG2神经胶质细胞的特定亚群。这些位于缺血后神经胶质瘢痕中的细胞处于活跃的细胞周期,并显示出与皮质星形胶质细胞相似的电流模式,可能是缺血后胶质瘢痕形成和修复过程中的重要参与者。NG2 glia display wide proliferation and differentiation potential under physiological and pathological conditions.Here,we examined these two features following different types of brain disorders such as focal cerebral ischemia(FCI),cortical stab wound(SW),and demyelination(DEMY)in 3-month-old mice,in which NG2 glia are labeled by tdTomato under the Cspg4 promoter.To compare NG2 glia expression profiles following different CNS injuries,we employed single-cell RT-qPCR and self-organizing Kohonen map analysis of tdTomato-positive cells isolated from the uninjured cortex/corpus callosum and those after specific injury.Such approach enabled us to distinguish two main cell populations(NG2 glia,oligodendrocytes),each of them comprising four distinct subpopulations.The gene expression profiling revealed that a subpopulation of NG2 glia expressing GFAP,a marker of reactive astrocytes,is only present transiently after FCI.However,following less severe injuries,namely the SW and DEMY,subpopulations mirroring different stages of oligodendrocyte maturation markedly prevail.Such injury-dependent incidence of distinct subpopulations was also confirmed by immunohistochemistry.To characterize this unique subpopulation of transient astrocytelike NG2 glia,we used single-cell RNA-sequencing analysis and to disclose their basic membrane properties,the patchclamp technique was employed.Overall,we have proved that astrocyte-like NG2 glia are a specific subpopulation of NG2 glia emerging transiently only following FCI.These cells,located in the postischemic glial scar,are active in the cell cycle and display a current pattern similar to that identified in cortical astrocytes.Astrocyte-like NG2 glia may represent important players in glial scar formation and repair processes,following ischemia.

关 键 词：星形胶质细胞 脱髓鞘 缺血 NG2胶质细胞 少突胶质细胞 刺伤 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]