La Jolla Interdisciplinary Neuroscience Center Cores - Stem Cell Core BU

干细胞核心 一、主要目标和新方向 干细胞核心将是一个新的设施。目前，还没有统一的干细胞核心设施来连接 La Jolla Torrey Pines台地的神经科学家。因此，这个干细胞设施将构成一个 新核心，以促进干细胞项目和圣地亚哥地区神经科学家之间的合作。 自从第一个人类胚胎干细胞的报告以来，人们对人类胚胎干细胞的兴趣稳步增长。 1998年上线。人类胚胎干细胞之所以有吸引力，是因为它们作为细胞治疗的潜力，或者直接取代 细胞或将其用作基因治疗的载体(Muller等人)。2006)。但细胞本身就是 本质上很有趣，因为它们具有多能性和自我更新的独特品质，而这些 这些特性重新引起了人们对基础细胞生物学的兴趣。HESC是完美的工具 研究人类神经发生过程中发生的事件，以了解正常发育和 以确定神经疾病期间哪里出了问题。HESC的多功能性意味着从 同一个群体可以产生多种细胞类型，然后可以用来解剖复杂的细胞 互动。例如，通过将HES细胞分化为运动神经元、骨骼肌细胞、 和星形胶质细胞，人们可以做混合配对实验来识别变性的关键成分 在肌萎缩侧索硬化症。通过使用移植的人类神经干细胞或通过产生人/鼠嵌合脑 从hESC衍生的神经元前体细胞，我们将有可能询问人类神经元对 阿尔茨海默病转基因模型中形成的淀粉样斑块。此外，HESCs将 最终被用于再生医学中的移植治疗。该核心设施建议 只使用经过批准的总统ES细胞系。所要求的资金特别重要，因为 71号提案原本是为加州的干细胞研究提供资金，但并未成为现实，目前正在 不清楚这些资金未来是否会变得可用。除人类胚胎干细胞外，这一核心将 允许La Jolla Torrey Pines台地的神经科学家获得有关使用小鼠的方法 (M)ES细胞。此外，干细胞核心拥有神经前体细胞(NPC)方面的专业知识 来源于HES和MES细胞。此外，从人胎脑和小鼠脑中提取的神经干细胞(获得 由BIMR和UCSD的工作人员)和成年啮齿动物NPC(来自弗雷德·盖奇的实验室，位于 索尔克研究所)将通过这个干细胞核心提供。所有这些细胞的起源 细胞系已获得机构批准和总统批准，必要时可用于 HESC系列。 干细胞核心的目的将是为干细胞提供培训和基本分析工具 在La Jolla Torrey Pines台地进行的细胞研究。目前，虽然有一家由NIH赞助的 伯纳姆医学研究所(BIMR)的干细胞中心，它针对的是特定的项目 而且不足以为想要使用它的当地神经科学家提供支持。有了这个 格兰特，我们建议利用BIMR经验丰富的干细胞中心教职员工 并扩大核心实验室的能力，使所有神经科学家都可以使用 La Jolla Torrey Pines台地地区(UCSD、Salk、BIMR和TSRI)。干细胞核心将被引导到 由Alexey Terskikh博士(BIMR，曾与著名干细胞欧文·魏斯曼教授一起训练) 斯坦福大学的专家。该设施的联席主管将是干细胞专家埃文·斯奈德博士和珍妮博士 洛林(在BIMR)，以及索尔克研究所的弗雷德(拉斯蒂)盖奇和胡安·卡洛斯·贝尔蒙特。 干细胞核心的总体目标是降低神经科学家涉及干细胞的障碍 通过提供来自经验丰富的干细胞生物学家的培训和专家建议，在他们的研究项目中提供对细胞的研究。 这将改善神经科学各个子专业的科学家之间的交流。 促进跨学科合作和创新方法。通过分享通用技术和 积累关于人类胚胎干细胞和体细胞(成人)干细胞基础生物学的知识 细胞，将会在时间、精力和成本上有相当大的节省。干细胞核心将发挥重要作用 确保用户与hESC方法的标准化保持同步的作用 由国际干细胞科学界呼吁(Andrews等人)。2005年；洛林2005年)。 这个核心的主要焦点是提供特定于干细胞的技术，这些技术将带来新的见解 在神经科学方面，并协助开发干细胞的临床应用。例如, 干细胞培养特性与移植后行为的相关性 帮助决定使用哪些电池以及需要采取哪些质量控制措施 临床应用。核心支持将包括胚胎干细胞和其他干细胞的培养、核型分析、SNP基因分型、 微阵列分析、干细胞和分化标记的免疫组织化学分析 多能性和分化，以及使用BIMR丰富的干细胞信息数据库。 此外，干细胞核心学院将为实验设计、数据分析、解释提供建议。 结果，并协助手稿和赠款申请。干细胞核心教职员工将 还担任博士后和年轻教职员工的导师，帮助他们发表文章并获得资助 支持。

STEM CELL CORE 1. MAIN OBJECTIVES AND NEW DIRECTIONS The Stem Cell Core will be a new facility. Currently, there is no unified Stem Cell Core Facility to link neuroscientists on the La Jolla Torrey Pines Mesa. Therefore, this Stem Cell facility will constitute a new Core to foster stem cell projects and collaborations among neuroscientists in the San Diego area. Interest in human embryonic stem cells (hESCs) has grown steadily since the report of the first hESC line in 1998. hESCs are attractive because of their potential as cell therapy, either directly replacing cells or by using them as vehicles for gene therapy (Muller et al. 2006). But the cells themselves are intrinsically interesting, because of their unique qualities of pluripotence and self-renewal, and these qualities have led to a resurgence of interest in fundamental cell biology. hESC are the perfect tools to study events that occur during human neurogenesis, both to understand normal development and to identify what goes wrong during neurological disease. The versatility of hESC means that from the same population one can generate multiple cell types that can then be used to dissect complex cellcell interactions. For example, by differentiating hES cells into motor neurons, skeletal muscle cells, and astroglia, one can do mix-and-match experiments to identify the vital components of degeneration in ALS. By generating human/mouse chimeric brains using transplanted human neural stem cells or neuronal precursors derived from hESC, it will be possible to ask how human neurons react to the amyloid plaques that develop in transgenic models of Alzheimer's disease. Additionally, hESCs will eventually be used for transplantation therapies in regenerative medicine. This Core facility proposes to use only approved Presidential ES cell lines. The funds requested are particularly important because Prop 71 which was to fund stem cell work in California has not become a reality, and it is currently not clear if these funds will become available in the future. In addition to hESCs, this core will allow neuroscientists on the La Jolla Torrey Pines Mesa access to methods regarding the use of murine (m)ES cells. Additionally, the Stem Cell Core has expertise with neural progenitor cells (NPCs) derived both from hES and mES cells. Moreover, NPCs from fetal human and mouse brains (obtained by workers at BIMR and UCSD), and adult rodent NPCs (from the laboratory of Fred Gage at The Salk Institute) will be available through this Stem Cell Core. The origins of all of these cells and cell lines have received both Institutional approval and Presidential approval, where necessary for hESC lines. The purpose of the Stem Cell Core will be to provide training and fundamental analysis tools for stem cell research throughout the La Jolla Torrey Pines Mesa. Currently, while there is an NIH-sponsored Stem Cell Center at the Burnham Institute for Medical Research (BIMR), it is aimed at specific projects and is insufficient to provide support for local neuroscientists who would like to use it. With this grant, we propose to take advantage of the BIMR's experienced Stem Cell Center faculty and staff and expand the capacity of the core laboratory to make the facilities available to all neuroscientists in the La Jolla Torrey Pines Mesa area (UCSD, Salk, BIMR and TSRI). The Stem Cell Core will be directed by Dr. Alexey Terskikh (BIMR, who trained with Prof. Irving Weismann, a well-known stem cell expert at Stanford. Co-directors of the facility will be stem cell experts Drs. Evan Snyder and Jeanne Loring (at BIMR), and Fred (Rusty) Gage and Juan Carlos Belmonte at The Salk Institute. The overall objective of the Stem Cell core is to lower the barrier for neuroscientists to involve stem cells in their research projects, by providing training and expert advice from experienced stem cell biologists. This will improve communication among scientists in a variety of neuroscience subspecialties to foster interdisciplinary collaborations and novel approaches. By sharing common techniques and accumulated knowledge about the fundamental biology of human ES cells and somatic (adult) stem cells, there will be a considerable savings in time, effort, and cost. The Stem Cell Core will play an important role in ensuring that the users are kept up to date with the standardization of hESC methods called for by the international stem cell scientific community (Andrews et al. 2005; Loring 2005). The principal focus of this core is to provide stem cell-specific technologies that will lead to new insights in neuroscience and aid in development of clinical applications for stem cells. For example, correlation of the characteristics of stem cells in culture and their behavior after transplantation will help in decisions about which cells to use and what quality control measures will be necessary for clinical use. Core support will include culturing of ES and other stem cells, karyotyping, SNP genotyping, microarray analysis, immunohistochemistry for stem cell and differentiation markers, assays for pluripotence and differentiation, and access to BIMR's extensive databases of stem cell information. In addition, the stem cell core faculty will offer advice for experimental design, data analysis, interpretation of results, and assistance with manuscripts and grant applications. Stem cell core faculty will also serve as mentors for postdocs and young faculty members, to help them publish and obtain grant support.