Regulation of adult progenitor cells and neural repair

脊髓损伤(SCL)是一种毁灭性的疾病，目前在美国约有20万人受到影响，每年约有1万例新诊断病例。脊髓损伤后，内源性祖细胞被激活，参与损伤区6‘7’8的部分修复。脊髓损伤后祖细胞分裂的解剖学来源目前是一个主要的研究重点。在这里，我们认为新的脊髓GILA是由分离的星形胶质细胞和少突胶质细胞产生的，产生aNPC谱系。我们假设，表皮生长因子(EGF)特异性地指导创伤脊髓损伤后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结果。首先，成人脊髓中的急性有丝分裂标记只显示了两类重要的分裂细胞：星形胶质细胞和少突胶质前体细胞。第二，脑室注射EGF选择性地促进少突胶质前体细胞的增殖，但不能促进星形胶质前体细胞的增殖。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。我们建议结合分子和组织学工具来确定EGF是否可以选择性地扩增脊髓损伤模型中的神经胶质前体细胞。目的探讨表皮生长因子(EGF)对脊髓损伤模型祖细胞增殖及分化后GILA净存活的影响。AIM II将描述对EGF有反应的一组不同的神经胶质前体细胞的命运。目的III研究EGF扩增的祖细胞在损伤后形成髓鞘的特征。这些研究将有助于更好地理解支配损伤后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.