CHARACTERIZATION OF NEURAL STEM CELLS IN THE ADULT BRAIN

描述（改编自申请人摘要）：新的神经元继续诞生 在成年哺乳动物脑室下区（SVZ）的外侧 脑室和海马齿状回的颗粒下层（SGL）。 神经干细胞，自我更新和产生神经元和神经胶质的细胞， 在体外用生长因子从SVZ和SGL中分离。存在 神经源性干细胞在成人大脑中的作用， 这些细胞为替代大脑提供了前所未有的机会， 细胞在损伤或疾病中丢失。最近的工作已经确定了SVZ干细胞 是B型细胞。B型细胞具有星形胶质细胞的结构并表达胶质细胞。 胶质酸性蛋白（GFAP）。为了了解 成年神经发生，有必要对细胞类型和细胞-细胞分类， 在这些germ区的相互作用，并描述了基因表达的 特定细胞类型。因此，我们提出以下具体目标：（1） 识别正在发育的SVZ的细胞类型和结构。初步 数据表明，细胞中含有一个专门的纤毛， 幼年动物的心室壁相当于心肌细胞中的B型细胞。 成年人了我们目前的实验来验证这一假设。(2)净化不同的 SVZ细胞类型并构建每种细胞类型的代表性cDNA文库。 这些文库将用于生成基因芯片阵列的探针， 成年SVZ主要细胞类型的基因表达。本实验 将与Affyoung合作进行。基因分析数据将是 通过互联网提供给科学界。这些数据将 揭示了SVZ细胞中存在的分子调控信号， 提供区分B型细胞与其他脑星形胶质细胞的标记物。（三） 探讨海马SGL的细胞类型和构筑。西格里 干细胞将使用类似于用于鉴定 SVZ干细胞初步结果表明，SGL干细胞具有 与SVZ B型细胞共同的性质。干细胞的综合知识 成年人大脑中两个主要的生发区的生物学将促进 利用成人来源的神经干细胞进行脑修复的能力。

DESCRIPTION(Adapted from applicant's abstract): New neurons continue to be born in the adult mammalian brain subventricular zone (SVZ) of the lateral ventricles and the subgranular layer (SGL) of the hippocampal dentate gyrus. Neural stem cells, cells that self-renew and generate neurons and glia, have been isolated from the SVZ and SGL with growth factors in vitro. The presence of neurogenic stem cells in the adult brain and the potential to manipulate these cells offers unprecedented opportunities for the replacement of brain cells lost in injury or disease. Recent work has identified the SVZ stem cell as Type B cell. Type B cells have the structure of astrocytes and express glial fibrillary acidic protein (GFAP). To understand the molecular regulation of adult neurogenesis, it is necessary to catalog the cell types and cell-cell interactions in these germinal zones, and describe the gene expression of the specific cell types. We thus propose the following Specific Aims: (1) To identify the cell types and architecture of the developing SVZ. Preliminary data suggests that cells containing a single specialized cilium in the ventricle walls of the juvenile animal are equivalent to the Type B cell in the adult. We present experiments to test this hypothesis. (2) To purify different SVZ cell types and construct representative cDNA libraries for each cell type. The libraries will be used to generate probes for GeneChip arrays to profile the gene expression of the major cell types of the adult SVZ. This experiment will be performed in collaboration with Affymetrix. Gene profiling data will be made available to the scientific community via the Internet. This data will reveal the molecular regulatory signals present in the SVZ cells as well as provide markers differentiating Type B cells from other brain astrocytes. (3) To investigate the cell types and architecture of the hippocampal SGL. The SGL stem cell will be identified using techniques similar to those used to identify the SVZ stem cell. Preliminary results suggest that SGL stem cells have properties in common with SVZ Type B cells. The combined knowledge of stem cell biology in the two major germinal regions of the adult brain will advance the ability to utilize adult-derived neural stem cells for brain repair.