Development of an Adult CNS Stem Cell Marking System

成人中枢神经系统干细胞标记系统的开发

• 批准号: 6868589
• 负责人: Gregory A. Elder
• 金额: $ 7.96万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-15 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6868589
• 关键词: biomarker; biotechnology; cell differentiation; cell proliferation; electron microscopy; gene induction /repression; gene rearrangement; genetic promoter element; genetic techniques; genetically modified animals; green fluorescent proteins; hippocampus; immunocytochemistry; laboratory mouse; mature animal; method development; neurogenesis; recombinase; stem cells; transcription factor

Neurogenesis continues in adult brain in discrete regions including the hippocampus and the subventricular zone. The exact functional significance of neurogenesis in adult hippocampus is still being debated. However altered hippocampal neurogenesis may play a pathophysiological role in a number of neuropsychiatric disorders. Presently progenitor cells in adult brain are most commonly identified by bromodeoxyuridine (BrdU) labeling and their fate followed with specific differentiation markers. However this methodology suffers several limitations including issues of sensitivity and permanence. Here we propose to use a green fluorescent protein (GFP) based transgenic system that utilizes the Cre recombinase site specific DNA recombination system and the lac repressor inducible/regulatable system to develop an efficient method for permanently marking nestin lineage CNS stem cells in adult brain. This system will allow the fate of nestin lineage stem cells to be followed indefinitely in adult brain irrespective of their differentiation along neuronal or non-neuronal lines.

成人大脑中的神经发生在包括海马体和脑室下区在内的离散区域中持续进行。成人海马神经发生的确切功能意义仍在争论中。然而，海马神经发生的改变可能在许多神经精神疾病中发挥病理生理学作用。 目前，成人大脑中的祖细胞最常通过溴脱氧尿苷（BrdU）标记来识别，并且它们的命运遵循特定的分化标记。然而，这种方法存在一些局限性，包括敏感性和持久性问题。在这里，我们建议使用基于绿色荧光蛋白（GFP）的转基因系统，该系统利用Cre重组酶位点特异性DNA重组系统和lac阻遏物诱导/调节系统来开发一种在成人大脑中永久标记巢蛋白谱系CNS干细胞的有效方法。该系统将允许巢蛋白谱系干细胞在成人大脑中无限期地被追踪，无论它们沿着神经元或非神经元系分化。