Conversion of fibroblasts to functional spinal motor neurons using defined factor

产品说明：哺乳动物的神经系统由许多不同的神经元亚型组成，每种亚型都有自己的表型和对退行性疾病的不同敏感性。虽然一些特定的神经元类型可以从完整的啮齿动物胚胎中分离出来，或者从干细胞中工程化用于翻译研究，但这些方法非常耗时，并且许多神经元亚型无法获得。转录因子介导的重编程可能为疾病建模和再生医学提供更直接的神经元生成途径，但目前尚不清楚这种方法是否可用于创建具有免疫效用的细胞。在这里，我们建议确定一组转录因子足以将成纤维细胞转化为功能性脊髓运动神经元。我们将描述重编程过程，并检查所得运动神经元的分子和功能特性，以确定其治疗潜力。这些研究将为神经退行性疾病的研究提供患者特异性运动神经元的可获得来源，证明特定的成体细胞类型可以使用定义的因子从体细胞直接产生，并机械地剖析定义的因子重编程过程。

DESCRIPTION: The mammalian nervous system is composed of a multitude of distinct neuronal subtypes, each with its own phenotype and differential sensitivity to degenerative disease. Although some specific neuronal types can be isolated from intact rodent embryos or engineered from stem cells for translational studies, these approaches are time-consuming and many neuronal subtypes are inaccessible. Transcription factor-mediated reprogramming might provide a more direct route to the generation of neurons for disease modeling and regenerative medicine, but it is currently unclear if this approach can be used to create cells with translationl utility. Here, we propose to identify a set of transcription factors sufficient to convert fibroblats into functional spinal motor neurons. We will characterize the reprogramming process and examine the molecular and functional properties of the resulting motor neurons in order to determine their therapeutic potential. These studies will provide an accessible source of patient-specific motor neurons for the study of neurodegenerative disease, demonstrate that specific adult cell types can be directly generated from somatic cells using defined factors, and mechanistically dissect the defined-factor reprogramming process.