CHARACTERIZATION OF NEURAL STEM CELLS IN THE ADULT BRAIN

描述(摘自申请者的摘要)：新神经元不断诞生 成年哺乳动物脑室下区外侧区(SVZ) 脑室和海马齿状回的颗粒下层(SGL)。 神经干细胞是一种自我更新并产生神经元和神经胶质的细胞，具有 在体外用生长因子从SVZ和SGL中分离得到。他的存在 成人脑中神经源性干细胞的数量和操纵的可能性 这些细胞为大脑的替代提供了前所未有的机会 细胞因损伤或疾病而丢失的细胞。最近的工作发现了SVZ干细胞 作为B型细胞。B型细胞具有星形细胞结构，表达胶质细胞 纤维酸性蛋白(GFAP)。要了解细胞因子的分子调控 成人神经发生，有必要对细胞类型和细胞-细胞进行分类 在这些生发区的相互作用，并描述了基因表达 特定的细胞类型。为此，我们提出以下具体目标：(一) 确定正在开发的SVZ的细胞类型和架构。初步 数据表明，含有单个特化纤毛的细胞 幼年动物的室壁相当于体内的B细胞。 成年人。我们通过实验来验证这一假设。(2)净化不同 SVZ细胞类型，并构建每种细胞类型的代表性cDNA文库。 这些库将用于为基因芯片阵列生成探针以进行分析 成体SVZ主要细胞类型的基因表达。这项实验 将与Affymetrix合作执行。基因图谱数据将是 通过互联网向科学界提供。此数据将 揭示SVZ细胞中存在的分子调控信号以及 提供区分B型细胞和其他脑星形细胞的标记。(3) 目的：研究大鼠海马SGL的细胞类型和构筑。SGL 干细胞将使用与用于鉴定的技术类似的技术进行鉴定 SVZ干细胞。初步结果表明，SGL干细胞具有 与SVZ类型B单元格相同的属性。干细胞的综合知识 成人大脑的两个主要生发区域的生物学将促进 利用成人来源的神经干细胞进行大脑修复的能力。

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.