美国加州大学洛杉矶分校Michael V. Sofroniew等研究人员合作揭示，小鼠脊髓损伤或中风后边界形成创伤修复星形胶质细胞的衍生和转录重编程。2024年6月21日，国际知名学术期刊《自然—神经科学》在线发表了这一成果。

研究人员发现脊髓损伤或中风后，90%和10%的边界形成星形胶质细胞分别来自于成年雌雄小鼠增殖的局部星形胶质细胞和少突胶质细胞祖细胞。时序转录组分析、单核RNA测序和免疫组化显示，中枢神经系统局灶性损伤后，局部成熟星形胶质细胞会发生去分化、增殖和转录重编程，形成永久性改变的新状态，与星形胶质细胞-神经元相互作用相关的分子持续下调，而与伤口愈合、微生物防御以及与基质细胞和免疫细胞相互作用相关的分子上调。

这些伤口修复星形胶质细胞在形态和转录上与脑膜周围限制性星形胶质细胞具有相同的特征，是神经保护边界的主要来源，通过将神经实质与基质细胞和免疫细胞分离，在病变周围重建中枢神经系统（CNS）的完整性，就像在整个健康的CNS中发生的那样。

据悉，CNS病变周围有新增殖的反应性星形胶质细胞形成的神经保护性边界；然而，人们对这些细胞的基本特征知之甚少。

附：英文原文

Title: Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice

Author: OShea, Timothy M., Ao, Yan, Wang, Shinong, Ren, Yilong, Cheng, Amy L., Kawaguchi, Riki, Shi, Zechuan, Swarup, Vivek, Sofroniew, Michael V.

Issue&Volume: 2024-06-21

Abstract: Central nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes; however, fundamental features of these cells are poorly understood. Here we show that following spinal cord injury or stroke, 90% and 10% of border-forming astrocytes derive, respectively, from proliferating local astrocytes and oligodendrocyte progenitor cells in adult mice of both sexes. Temporal transcriptome analysis, single-nucleus RNA sequencing and immunohistochemistry show that after focal CNS injury, local mature astrocytes dedifferentiate, proliferate and become transcriptionally reprogrammed to permanently altered new states, with persisting downregulation of molecules associated with astrocyte–neuron interactions and upregulation of molecules associated with wound healing, microbial defense and interactions with stromal and immune cells. These wound repair astrocytes share morphologic and transcriptional features with perimeningeal limitans astrocytes and are the predominant source of neuroprotective borders that re-establish CNS integrity around lesions by separating neural parenchyma from stromal and immune cells as occurs throughout the healthy CNS.

DOI: 10.1038/s41593-024-01684-6

Source: https://www.nature.com/articles/s41593-024-01684-6