REGULATION OF POSTNATAL CORTICAL MULTIPOTENT PROGENITORS

我们已经从大脑皮层分离出多能祖细胞 高峰期不受脑室周围生殖区影响 出生后早期的神经胶质形成。这些祖先物种经历了 表皮对细胞体外扩增和自我更新的影响 生长因子，并能产生神经元和神经胶质细胞，包括髓鞘 表达蛋白质的少突胶质细胞。神经胶质祖细胞来源于 这些多能祖细胞表达神经营养素-3受体trkC， 神经营养因子-3的应用选择性地促进血管的扩张 需要额外环境的少突胶质祖细胞 少突胶质细胞的信号(睫状神经营养因子) 差异化。神经营养素-3还可以诱导血管内皮细胞的表达 皮质来源的神经胶质前体细胞上的CNTFpha受体 多能细胞，而骨形态发生蛋白促进 星形胶质细胞的产生并诱导trkC在这些细胞上的表达 祖先物种。在初步的活体研究中，我们还表明 移植的皮质多能细胞可以经历细胞 并产生神经胶质细胞和神经元的后代。此外, 从这些多能细胞中分离出的神经胶质前体细胞在 并产生少突胶质细胞和星形胶质细胞。皮质损伤 促进祖细胞的增殖和分化。离体 分析：1.定义表皮生长的细胞特性 因子反应性皮质多能祖细胞及其子代： 答：这些祖细胞会经历长期的自我更新吗？B.什么是 从这些多能神经派生的神经谱系物种的组成 细胞？C.神经营养因子-3的细胞作用是什么 少突胶质细胞和星形胶质细胞在神经胶质前体细胞中的发育 从这些多能细胞中衍生出来的？体内分析：2.定义 适当的出生后早期微环境信号的存在 对于皮质祖细胞发育：A.是否为细胞型 祖细胞扩张、谱系限制和分化 体外和体内的等效性？B.是神经胶质受限的后代 在体内具有双能性？C.中枢神经轴突的不同区域是否促进 不同的祖细胞反应特征？ 这些研究将加深我们对早期祖细胞的理解 正常哺乳动物神经谱系发育中的调节事件 大脑皮层成熟，确定潜在的病理机制 一系列遗传性和获得性神经障碍，并促进 开发新的再生策略。

We have isolated multipotent progenitor cells from the cerebral cortex independent of periventricular generative zones during the peak period of early postnatal gliogenesis. These progenitor species undergo cellular expansion and self-renewal in vitro in response to epidermal growth factor and can generate neurons and glia, including myelin protein-expressing oligodendrocytes. Glial progenitors derived from these multipotent progenitors express the neurotrophin-3 receptor, trkC, and application of neurotrophin-3 selectively promotes the expansion of oligodendrocyte progenitors that require additional environmental signals (ciliary neurotrophic factor, CNTF) for oligodendrocyte differentiation. Neurotrophin-3 can also induce the expression of the CNTFalpha receptor on glial progenitors derived from cortical multipotent cells, while bone morphogenetic proteins promote the generation of astrocytes and induce the expression of trkC on these progenitor species. In preliminary in vivo studies, we have also shown that transplanted cortical multipotent cells can undergo cellular expansion and give rise to glial and neuronal progeny. In addition, glial progenitors isolated from these multipotent cells proliferate in vivo and give rise to oligodendrocytes and astrocytes. Cortical injury enhances progenitor cell expansion and differentiation. In vitro analysis: 1. To define the cellular properties of epidermal growth factor-responsive cortical multipotent progenitors and their progeny: A. Do these progenitors undergo long-term self-renewal? B. What is the composition of neural lineage species derived from these multipotent cells? C. What are the cellular actions of neurotrophin-3 on oligodendroglial and astroglial development from glial progenitors derived from these multipotent cells? In vivo analysis: 2. To define the presence of appropriate early postnatal microenvironmental signals for cortical progenitor cell development: A. Are the cellular profiles of progenitor expansion, lineage restriction and differentiation equivalent in vitro and in vivo? B. Are glial-restricted progeny bipotent in vivo? C. Do different areas of the CNS neuraxis promote distinct progenitor cell response profiles? These studies will further our understanding of early progenitor cell regulatory events in neural lineage development during normal mammalian cerebral cortical maturation, identify pathologic mechanisms underlying a range of genetic and acquired neurologic disorders, and promote the development of novel regenerative strategies.