Prospective Purification of Adult Stem Cell Astrocytes

成体干细胞星形胶质细胞的前瞻性纯化

• 批准号: 8658860
• 负责人: MICHAEL L SHELANSKI
• 金额: $ 34.65万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658860
• 关键词: Adult; Aging; Astrocytes; Back; Behavior; Blocking Antibodies; Brain; Cell Cycle; Cell Cycle Kinetics; Cells; Data; Development; Disease; Epidermal Growth Factor Receptor; Equilibrium; Exhibits; Fluorescence-Activated Cell Sorting; Gene Expression Profiling; Genetic; Glial Fibrillary Acidic Protein; Goals; Homeostasis; In Vitro; Infusion procedures; Label; Lead; Long-Term Effects; Measures; Mediating; Mediator of activation protein; Molecular; Molecular Profiling; Mus; Natural regeneration; Neuroglia; Neurons; Oligodendroglia; PDGFRB gene; Platelet-Derived Growth Factor beta Receptor; Population; Property; Proto-Oncogene Proteins c-sis; Recruitment Activity; Regulation; Role; Signal Transduction; Stem cells; Testing; adult stem cell; base; brain repair; cell behavior; in vivo; insight; lateral ventricle; nerve stem cell; neurogenesis; novel; olfactory bulb; prominin; prospective; research study; self-renewal; subventricular zone

DESCRIPTION (provided by applicant): Stem cells continuously generate new neurons in restricted regions of the adult mammalian brain. The subventricular zone (SVZ) is the largest germinal region in the adult gives rise to neurons that migrate to the olfactory bulb as well as some oligodendrocytes. The in vivo stem cells are a subset of astrocytes, glial cells classically associated with support functions. These endogenous stem cells potentially represent a pool of cells that can be harnessed for brain repair. A balance between intrinsic and extrinsic signals mediates the activation of quiescent stem cells. However, the ability to distinguish between quiescent and activated stem cells has been hampered by a lack of markers. Here we identify a combination of markers that allow us to identify and isolate four populations of astrocytes from the SVZ directly from the in vivo niche. Based on cell cycle analysis, in vitro stem cell behavior and gene expression profiling, we hypothesize that they correspond to quiescent stem cell astrocytes, activated stem cell astrocytes and niche astrocytes. We propose to: 1) Define the cell cycle kinetics of the purified astrocyte populations, and their ability to act as stem cells in vitro, as well as how their numbers and functional properties change with aging, 2) perform lineage tracing of quiescent and activated stem cells under homeostasis and during regeneration and 3) define the role of PDGFRb in regulating adult neural stem cell quiescence. Together these studies will yield key insights into the regulation of stem cell quiescence in the adult brain.

描述（由申请人提供）：干细胞在成年哺乳动物大脑的有限区域中持续产生新的神经元。室管膜下区（SVZ）是成年人最大的嗅球区，产生迁移到嗅球的神经元以及一些少突胶质细胞。体内干细胞是星形胶质细胞的一个子集，胶质细胞经典地与支持功能相关。这些内源性干细胞可能代表了一个可以用于大脑修复的细胞库。内在和外在信号之间的平衡介导静止干细胞的激活。然而，由于缺乏标记物，区分静止和活化干细胞的能力受到阻碍。在这里，我们确定了一个组合的标志物，使我们能够识别和分离四个群体的星形胶质细胞直接从SVZ在体内的小生境。基于细胞周期分析，体外干细胞行为和基因表达谱，我们假设它们对应于静止的干细胞星形胶质细胞，激活的干细胞星形胶质细胞和小生境星形胶质细胞。我们建议：1）定义纯化的星形胶质细胞群体的细胞周期动力学，及其在体外充当干细胞的能力，以及它们的数量和功能特性如何随着衰老而变化，2）在稳态和再生期间对静止和活化的干细胞进行谱系追踪和3）定义PDGFRb在调节成人神经干细胞静止中的作用。总之，这些研究将产生对成人大脑干细胞静止调节的关键见解。