Genomic analysis of reactive astrogliosis.
Genomic analysis of reactive astrogliosis.
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DOI：
10.1523/jneurosci.6221-11.2012
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发表时间：
2012-05-02
期刊：
影响因子：
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通讯作者：
Barres BA
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文献类型：
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作者：
Zamanian JL;Xu L;Foo LC;Nouri N;Zhou L;Giffard RG;Barres BA
反应性星形胶质细胞增生的特征是星形胶质细胞表型在应对所有中枢神经系统损伤和疾病时发生显著变化。为了更好地理解反应性星形胶质细胞的状态，我们使用了Affymetrix基因芯片阵列来分析在使用两种小鼠损伤模型（缺血性中风和神经炎症）诱导后的不同时间点分离出的反应性星形胶质细胞群体中的基因表达情况。我们发现反应性胶质细胞增生包括在损伤后基因表达的快速诱导，但这种诱导很快减弱，并确定了两个诱导基因，Lcn2和Serpina3n，作为反应性星形胶质细胞的强标志物。令人惊讶的是，反应性星形胶质细胞表型强烈依赖于诱导损伤的类型。尽管在两种损伤模型的反应性星形胶质细胞中都有一组核心基因上调，但至少50%的基因表达改变是特定于某种给定的损伤类型的。缺血中的反应性星形胶质细胞表现出一种分子表型，表明它们可能是有益的或具有保护作用，而由脂多糖诱导的反应性星形胶质细胞表现出一种表明它们可能有害的表型。这些发现表明，尽管存在已确定的共性，但星形胶质细胞反应性胶质细胞增生是一种高度异质性的状态，其中星形胶质细胞的活动发生改变以应对特定的损伤。这就提出了一个问题：存在多少种反应性星形胶质细胞亚型？我们的发现为两种反应性星形胶质细胞亚型提供了转录组数据库，这将对产生关于它们功能的新的可检验假设以及为检测人类神经系统疾病中不同类型的反应性星形胶质细胞提供新的标志物非常有用。
Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two mouse injury models, ischemic stroke and neuroinflammation. We find reactive gliosis consists of a rapid, but quickly attenuated induction of gene expression after insult and identify two induced genes, Lcn2 and Serpina3n, as strong markers of reactive astrocytes. Strikingly, reactive astrocyte phenotype strongly depended on the type of inducing injury. Although there is a core set of genes that is up-regulated in reactive astrocytes from both injury models, at least 50% of the altered gene expression is specific to a given injury type. Reactive astrocytes in ischemia exhibited a molecular phenotype that suggests that they may be beneficial or protective, whereas reactive astrocytes induced by LPS exhibited a phenotype that suggests that they may be detrimental. These findings demonstrate that, despite well established commonalities, astrocyte reactive gliosis is a highly heterogeneous state in which astrocyte activities are altered to respond to the specific injury. This raises the question of how many subtypes of reactive astrocytes exist. Our findings provide transcriptome databases for two subtypes of reactive astrocytes that will be highly useful in generating new and testable hypotheses of their function, as well as for providing new markers to detect different types of reactive astrocytes in human neurological diseases.