Functional roles of astrocytes in modulating neural stem and progenitor cells in the adult mammalian spinal cord

成年哺乳动物脊髓缺乏自我修复能力，尽管脊髓内存在组织特异性神经干细胞(NSCs)。在发育过程中，神经干细胞显示出分化为包括神经元、星形胶质细胞和少突胶质细胞在内的所有类型脊髓细胞并构建脊髓的能力。然而，在成年脊髓中，神经干细胞的再生活性受到明显的限制。有趣的是，来自我们和其他研究人员的证据表明，成人脊髓损伤导致有限的少突胶质细胞替代，这是一种在脊髓神经纤维周围产生髓鞘所需的神经胶质细胞类型。这些发现强烈表明，存在严格调控成年脊髓内神经干细胞先天潜能的环境因素。到目前为止，我们对成年神经干细胞在其脊髓环境中调节特性的事件只有很少的了解。我们的目标是了解脊髓神经干细胞在正常和疾病条件下对环境变化的动态反应。在这项提案中，我和我的团队将重点研究星形胶质细胞及其分泌因子在控制发育中和成年脊髓中内源性神经干细胞特性方面的影响。星形胶质细胞是脊髓的支持细胞，在脊髓生物学的许多方面发挥着关键作用。星形胶质细胞分泌大量细胞因子和生长因子，既有促进作用，也有抑制作用，可以影响神经干细胞的行为。从这项研究中获得的知识将为脊髓研究提供新的基础知识，并为加强脊髓损伤和多发性硬化症等疾病的内源性修复和再生提供新的靶点。重要的是，这项研究计划还将为本科生和研究生以及初级研究员提供一个独特的机会，以获得神经科学和干细胞研究方面的高度重视的专业知识，并发展进行独立科学研究的技能。

Adult mammalian spinal cord lacks the ability for self repair despite the presence of tissue-specific neural stem cells (NSCs) inside the spinal cord. During the developmental growth, NSCs show the capacity to give rise to all types of spinal cord cells including neurons, astrocytes and oligodendrocytes and build the spinal cord. However, in the adult spinal cord, the regenerative activity of NSCs is significantly restricted. Interestingly, evidence from our research and that of others demonstrates that injuries to the adult spinal cord result in limited oligodendroglial cell replacement, a glial cell type required for generating myelin sheath around the spinal cord nerve fibers. These findings strongly suggest the presence of environmental factors that tightly regulate the innate potential of NSCs within the adult spinal cord. To date, we have only a poor understanding of the events that modulate the properties of adult NSCs within their spinal cord environment. Our goal is to understand the dynamic responses of spinal cord NSCs to changing their environment under both normal and disease conditions. In this proposal, my team and I will focus on the impact of astrocytes and their secreted factors in controlling the properties of endogenous NSCs in the developing and adult spinal cord. Astrocytes are support cells of the spinal cord that play pivotal roles in many aspects of spinal cord biology. Astrocytes secrete a host of cytokines and growth factors with both promoting and inhibitory nature that can influence the behaviour of NSCs. The knowledge to be gained from this research will provide new fundamental knowledge in spinal cord research and novel targets for enhancing endogenous repair and regeneration in conditions such as spinal cord injuries and multiple sclerosis. Importantly, this research program will also provide a unique opportunity for undergraduate and graduate students as well as junior researcher to gain highly valued expertise in neuroscience and stem cell research and to develop the skills to perform independent scientific research.