Are astrocytes multifunctional or classified into diverse lineages?

在脊椎动物中枢神经系统(CNS)中，星形胶质细胞执行多种功能来支持神经活动：包括向神经元提供营养物质、神经递质的循环和血脑屏障的形成。除了它们的经典作用，最近的研究表明，神经胶质细胞广泛参与突触发生和突触活动的调节。然而，星形胶质细胞是否可以根据其特定的功能被划分为差异很大的细胞谱系，目前还知之甚少。如果是这样的话，星形胶质细胞亚系承诺的机制和时间是有趣的课题。或者，星形胶质细胞可能是一个同质的细胞群体，并根据其所处的局部环境改变其功能。为了解决这个问题，我们建立了一个携带胶质纤维酸性蛋白(GFAP)基因“loxP-nlacZ-loxP-GAP43GFP”的GFAP/Cre报告小鼠品系。在这只小鼠中枢神经系统中，只有祖细胞表达cre重组酶的星形胶质细胞亚系表达GAP43GFP。作为第一步，GFAP/loxP报告小鼠与Emx1-Cre KiΔneo小鼠(由岩里博士和岩原博士提供)杂交，标记Emx1阳性的帕利氏祖细胞来源的星形胶质细胞为绿色荧光蛋白+细胞。皮质板区星形胶质细胞以β半乳糖/绿色荧光蛋白阳性为主，中线胶质细胞亚群为β半乳糖/绿色荧光蛋白阳性，提示不同来源的皮质星形胶质细胞和中线胶质细胞功能不同。为了进一步研究大脑皮质和海马区GFAP+细胞的独特功能，使用细胞分选器分离它们并进行基因表达微阵列分析。海马区GFAP+细胞表达神经前体细胞和未成熟神经元特有的几个基因。

In the vertebrate central nervous system (CNS), astrocytes perform multiple functions to support neural activities: including provision of neutrients to neurons, recycling of neurotransmitters and formation of blood brain barrier. In addition to their classical roles, recent studies have demonstrated that glial cells are widely involved in the regulation of synaptogenesis and synaptic activities. However, it has been poorly understood whether astrocytes can be classified into widely divergent cell lineages with their specific functions. If so, the mechanisms and timing of astrocyte sub-lineage commitments are interesting subjects. Alternatively, astrocytes may be a homogeneous cell population and adopt to change their functions according to their local environment. To challenge this question, we established a GFAP/Cre-reporter mouse line that carries the "loxP-nlacZ-loxP-GAP43GFP" cassette in glial fibrillary acidic protein (GFAP) gene locus. In this mouse CNS, only a sub-lineage of astrocytes, whose ancestral progenitor cells express cre recombinase, express GAP43GFP. As a first step, the GFAP/loxP-reporter mice were crossbred with Emx1-Cre KI Δneo mice (provided by Drs. Iwasato and Itohara) to label Emx1-positive pallial progenitors-derived astorocytes as GFP+ cells. Most astrocytes in cortical plate were βGal-/GFP+, while a subpopulation of midline glia that guided corpus callosum formation were βGal+/GFP-, suggesting that functionally different cortical astrocytes and midline glia were generated from different origins. To further investigate unique functions, if any, for the cortical and hippocampal GFAP+ cells, they were isolated using cell sorter and subjected for gene expression microarray analysis. Hippocampal GFAP+ cells expressed several genes characteristic of neural progenitor cells and immature neurons.