Olig 2 Lineage Cells Derived From ES Cells

来自 ES 细胞的 Olig 2 谱系细胞

• 批准号: 7217978
• 负责人: DAVID I GOTTLIEB
• 金额: $ 30.19万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7217978
• 关键词: Achievement; Antibodies; Astrocytes; BMP2 gene; BMP4; Basic Science; Biological Process; Cell Count; Cell Lineage; Cell Transplantation; Cell division; Cell physiology; Cells; Ciliary Neurotrophic Factor; Commit; Data; Development; EGF gene; ES Cell Line; Erinaceidae; FGF8 gene; Fibroblast Growth Factor 2; Fibroblast Growth Factor 8; Gene Expression; Gene Expression Profiling; Genes; Glial Differentiation; Goals; Green Fluorescent Proteins; In Vitro; Knock-in Mouse; Learning; Life; Maps; Measures; Mitogens; Modeling; Motor Neurons; Multipotent Stem Cells; Nervous system structure; Neuroglia; Neuronal Differentiation; Neurons; Numbers; Oligodendroglia; Pathway interactions; Platelet-Derived Growth Factor; Population; Protocols documentation; Reagent; Research; Reverse Transcriptase Polymerase Chain Reaction; SHH gene; Serum; Signal Transduction; Source; Specific qualifier value; Staging; Staining method; Stains; Stem cells; System; Testing; Time; To specify; Transplantation; Tretinoin; Work; autocrine; base; bone morphogenetic protein 4; embryonic stem cell; genetic manipulation; genetically modified cells; in vivo; insight; mRNA Expression; member; nerve stem cell; neurodevelopment; practical application; precursor cell; progenitor; receptor; relating to nervous system; research study; response; tool

The long-term goal of this research is two-fold. One is to gain insights into the mechanisms that control fate choice in the early developing nervous system. The principal tool is ES cells differentiated in culture to produce a model of normal CNS development. The model is powerful because large numbers of cells are produced and because gone targeting and other genetic manipulations are feasible. Using the advantages of this model we will investigate how early neural precursor cells choose a fate defined by expression of the Olig2 gene. Cells from this pathway eventually differentiate into motor neurons and oligodendrocytes. Retinoic acid and sonic hedgehog interact to specify na'ive cells to follow this fate. We will learn how these 2 pathways interact. Specified cells are capable of cell division. We have discovered how to induce dividing cells to undergo long-term division. Even though they divide continuously the cells keep their identity as members of the Olig2 lineage. Our working hypothesis is that normal early neural stem cells are indeed capable of sustained division. If true, this will provide large numbers of specified neural stem cells for many applications. The final stage of stem cell life is differentiation. We will investigate signals that are responsible for differentiation of Olig2 pathway cells. We have already discovered how to efficiently differentiate these cells into astrocytes and oligodendrocytes and will extend this work to neurons. The second long-term goal is to harness the potential that ES cells have for neural transplantation. While the potential is real, practical application demands major advances in basic understanding. It is theoretically possible to direct ES cells to coordinately differentiate into any single type of neural cell. Achievement of this goal even for a few cell lineages would open up new opportunities in transplantation research. Results of this project will provide proof-of-principle for this idea. A combination of instructive and selective strategies is being applied to the goal of getting pure populations. Cells from each stage of the Olig2 lineage will be available in large numbers and at high purity. Lessons learned from this lineage will be applicable to others. One strong possibility is that genetically engineered cells will be most efficacious in transplantation. The ES cell-based system is ideally suited to providing genetically engineered cells.

The long-term goal of this research is two-fold. One is to gain insights into the mechanisms that control fate choice in the early developing nervous system. The principal tool is ES cells differentiated in culture to produce a model of normal CNS development.该模型之所以强大，是因为产生了大量细胞，并且目标定位和其他基因操作都是可行的。 Using the advantages of this model we will investigate how early neural precursor cells choose a fate defined by expression of the Olig2 gene. Cells from this pathway eventually differentiate into motor neurons and oligodendrocytes. Retinoic acid and sonic hedgehog interact to specify na'ive cells to follow this fate. We will learn how these 2 路径相互作用。 Specified cells are capable of cell division.我们已经发现了如何诱导分裂细胞进行长期分裂。 Even though they divide continuously the cells keep their identity as members of the Olig2 lineage. Our working hypothesis is that normal early neural stem cells are indeed capable of sustained division. If true, this will provide large numbers of specified neural stem cells for many applications. The final stage of stem cell life is differentiation. We will investigate signals that are responsible for differentiation of Olig2 pathway cells. We have already discovered how to efficiently differentiate these cells into astrocytes and oligodendrocytes and will extend this work to neurons. The second long-term goal is to harness the potential that ES cells have for neural transplantation.虽然 潜力是真实的，实际应用需要在基本理解上取得重大进展。理论上，引导 ES 细胞协调分化成任何单一类型的神经细胞是可能的。即使对于少数细胞谱系而言，这一目标的实现也将为移植研究开辟新的机会。 Results of this project will provide proof-of-principle for this idea.指导性和选择性策略的结合正在被应用于获得纯种群的目标。来自 Olig2 谱系各个阶段的细胞将大量且高纯度地提供。从这一血统中吸取的教训将适用于其他血统。一种很大的可能性是基因工程细胞在移植中最有效。 ES 基于细胞的系统非常适合提供基因工程细胞。