Regulation of adult progenitor cells and neural repair

脊髓损伤（SCI）是目前影响美国约200，000人的破坏性病症，每年4，5诊断出约10，000个新病例。在脊髓损伤后，内源性祖细胞被激活并参与损伤区6'7'8的部分恢复。脊髓损伤后分裂祖细胞的解剖学来源是目前研究的主要焦点。在这里，我们提出，新的脊髓神经胶质细胞是从单独的星形胶质细胞和少突胶质细胞产生的aNPC谱系。我们假设表皮生长因子（EGF）特异性地指导创伤性脊髓损伤后由激活的祖细胞形成少突胶质细胞谱系。这一假设基于以下观察。首先，急性有丝分裂标记在成人脊髓揭示只有两个重要的群体分裂细胞：星形胶质细胞和少突胶质细胞祖细胞。第二，脑室内注入EGF选择性地增加少突胶质细胞祖细胞的增殖，但不增加星形胶质细胞祖细胞的增殖。第三，EGF扩增的祖细胞的命运测定显示新的少突胶质细胞增加，但新的星形胶质细胞的数量没有变化。我们建议使用分子和组织学工具的组合，以确定是否EGF可以选择性地扩增胶质祖细胞在SCI模型。目的探讨表皮生长因子（EGF）对脊髓损伤后神经祖细胞增殖及分化胶质细胞存活的影响。目的II将描述一个独特的群体的神经胶质祖细胞的命运，对表皮生长因子的反应。目的III将表征损伤后EGF扩增的祖细胞形成髓鞘。这些研究将导致更好地了解损伤后控制干细胞命运的分子控制，并可能揭示诱导细胞再生的新机制。

Spinal cord injury (SCl) is a devastating condition currently affecting approximately 200,000 people in the United States, with approximately 10,000 new cases diagnosed each year 4'5. Following injury to the spinal cord, endogenous progenitor cells are activated and participate in a partial restoration of the injury zone 6'7'8. The anatomical source of dividing progenitor cells following spinal cord lesion is now a major focus of study. Here we propose that new spinal cord gila are generated from separate astrocyte and oligodendrocyte producing aNPC lineages. We hypothesize that epidermal growth factor (EGF) specifically directs the formation of the oligodendrocyte lineage from activated progenitor cells following traumatic spinal cord injury. This hypothesis is based on the following observations. First, acute mitotic labeling in the adult spinal cord reveals only two significant populations of dividing cells: astrocyte and oligodendrocyte progenitor cells. Second, EGF infused intraventricularly selectively increases the proliferation of oligodendrocyte progenitor cells but not astrocyte progenitor cells. Thirdly, fate determination of EGF expanded progenitor cells shows an increase in new oligodendrocytes but no change in the number of new astrocytes. We propose to use a combination of molecular and histological tools to determine if EGF can selectively amplify glial progenitor cells in a model of SCI. Aim I will determine the effect of EGF on proliferation of progenitor cells and net survival of differentiated gila in a model of spinal cord trauma. Aim II will characterize the fate of a distinct population of glial progenitor cells that respond to EGF. Aim III will characterize the formation of myelin by EGF expanded progenitor cells following injury. These studies will lead to a better understanding of the molecular controls that govern stem cell fate following injury and potentially reveal a novel mechanism for inducing cellular regeneration.