Conversion of Fibroblasts to fxnal Spinal Motor Neurons Using Defined Factor

摘要 哺乳动物的神经系统由许多不同的神经元亚型组成，每种亚型具有 其自身表型和对变性疾病的不同敏感性。虽然某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，也可以从干细胞中工程化，用于翻译研究，这些 这些方法是耗时的，并且许多神经元亚型是不可接近的。转录因子介导 重新编程可能为疾病建模提供更直接的神经元生成途径， 再生医学，但目前还不清楚这种方法是否可以用来创造细胞与翻译 效用在这里，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，并检查分子 和功能特性，以确定它们的治疗潜力。 这些研究将提供一个患者特异性运动神经元的来源，用于研究 神经退行性疾病，证明了特定的成体细胞类型可以直接从体细胞生成。 细胞使用定义的因素，并机械解剖定义的因素重编程过程。

Abstract 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 translational utility. Here, we propose to identify a set of transcription factors sufficient to convert fibroblasts 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.