Are astrocytes multifunctional or classified into diverse lineages?

在脊椎动物中枢神经系统（CNS）中，星形胶质细胞具有多种功能以支持神经活动：包括向神经元提供营养物质、回收神经递质和形成血脑屏障。近年来的研究表明，神经胶质细胞除了具有经典的作用外，还广泛参与突触发生和突触活动的调节。然而，它一直知之甚少，是否星形胶质细胞可以分为广泛不同的细胞谱系与其特定的功能。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主题。或者，星形胶质细胞可能是一个同质的细胞群体，并根据其局部环境改变其功能。为了挑战这个问题，我们建立了GFAP/Cre报告基因小鼠系，其在胶质纤维酸性蛋白（GFAP）基因座中携带“loxP-nlacZ-loxP-GAP 43 GFP”盒。在该小鼠CNS中，仅星形胶质细胞的亚系表达GAP 43 GFP，其祖先祖细胞表达cre重组酶。作为第一步，将GFAP/loxP报告基因小鼠与Emx 1-Cre KI Δneo小鼠（由Iwasato和Itohara博士提供）杂交，以将Emx 1阳性苍白球祖细胞衍生的星形细胞标记为GFP+细胞。皮质板中的大多数星形胶质细胞为βGal-/GFP+，而引导胼胝体形成的中线胶质细胞亚群为βGal+/GFP-，表明皮质星形胶质细胞和中线胶质细胞来源不同。为了进一步研究皮质和海马GFAP+细胞的独特功能（如果有的话），使用细胞分选仪分离它们并进行基因表达微阵列分析。海马GFAP+细胞表达神经前体细胞和未成熟神经元的几种基因特征。

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.