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成年小鼠皮层中NG2胶质细胞的星形胶质细胞样亚群具有神经祖细胞的特征。

Astrocyte-like subpopulation of NG2 glia in the adult mouse cortex exhibits characteristics of neural progenitor cells.

作者信息

Janeckova Lucie, Knotek Tomas, Kriska Jan, Hermanova Zuzana, Kirdajova Denisa, Kubovciak Jan, Berkova Linda, Tureckova Jana, Camacho Garcia Sara, Galuskova Katerina, Kolar Michal, Anderova Miroslava, Korinek Vladimir

机构信息

Laboratory of Cell and Developmental Biology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.

Department of Cellular Neurophysiology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.

出版信息

Glia. 2024 Feb;72(2):245-273. doi: 10.1002/glia.24471. Epub 2023 Sep 29.

Abstract

Glial cells expressing neuron-glial antigen 2 (NG2), also known as oligodendrocyte progenitor cells (OPCs), play a critical role in maintaining brain health. However, their ability to differentiate after ischemic injury is poorly understood. The aim of this study was to investigate the properties and functions of NG2 glia in the ischemic brain. Using transgenic mice, we selectively labeled NG2-expressing cells and their progeny in both healthy brain and after focal cerebral ischemia (FCI). Using single-cell RNA sequencing, we classified the labeled glial cells into five distinct subpopulations based on their gene expression patterns. Additionally, we examined the membrane properties of these cells using the patch-clamp technique. Of the identified subpopulations, three were identified as OPCs, whereas the fourth subpopulation had characteristics indicative of cells likely to develop into oligodendrocytes. The fifth subpopulation of NG2 glia showed astrocytic markers and had similarities to neural progenitor cells. Interestingly, this subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression profile changed after ischemia, with increased numbers of genes related to neurogenesis. Immunohistochemical analysis confirmed the temporal expression of neurogenic genes and showed an increased presence of NG2 cells positive for Purkinje cell protein-4 at the periphery of the ischemic lesion 12 days after FCI, as well as NeuN-positive NG2 cells 28 and 60 days after injury. These results suggest the potential development of neuron-like cells arising from NG2 glia in the ischemic tissue. Our study provides insights into the plasticity of NG2 glia and their capacity for neurogenesis after stroke.

摘要

表达神经元胶质抗原2(NG2)的胶质细胞,也被称为少突胶质前体细胞(OPC),在维持大脑健康方面发挥着关键作用。然而,人们对它们在缺血性损伤后分化的能力了解甚少。本研究的目的是探究缺血性脑内NG2胶质细胞的特性和功能。我们使用转基因小鼠,在健康大脑以及局灶性脑缺血(FCI)后,选择性地标记表达NG2的细胞及其后代。利用单细胞RNA测序,我们根据基因表达模式将标记的胶质细胞分为五个不同的亚群。此外,我们使用膜片钳技术检测了这些细胞的膜特性。在鉴定出的亚群中,三个被鉴定为OPC,而第四个亚群具有表明可能发育为少突胶质细胞的细胞特征。NG2胶质细胞的第五个亚群显示出星形胶质细胞标志物,并且与神经祖细胞有相似之处。有趣的是,这个亚群在健康组织和缺血后组织中均存在;然而,其基因表达谱在缺血后发生了变化,与神经发生相关的基因数量增加。免疫组织化学分析证实了神经发生相关基因的时间表达,并显示在FCI后12天,缺血性病变周边Purkinje细胞蛋白-4阳性的NG2细胞数量增加,以及在损伤后28天和60天出现NeuN阳性的NG2细胞。这些结果表明缺血组织中NG2胶质细胞可能发育为神经元样细胞。我们的研究为NG2胶质细胞的可塑性及其在中风后的神经发生能力提供了见解。

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