Generating neurons through cellular reprogramming

描述（由申请人提供）：转录因子重新编程细胞身份的能力通常非常有限，并且妨碍了我们为各种不同应用生成细胞类型的能力。在这项题为“通过细胞重编程生成神经元”的拨款提案中，我们建议在线虫中进行遗传筛选。秀丽隐杆线虫将识别通常阻止转录因子重编程细胞身份的能力的因子。在前期工作中，确定了两个这样的“重编程制动器”。进一步的基因筛选可能会揭示更多的重编程抑制剂，并帮助我们更好地了解细胞的可塑性，特别是神经元的身份。该拨款提案具体使用线虫模型系统作为基因发现工具。 公共健康相关性：该研究提案研究了个体细胞身份重新编程的分子机制。从概念上讲，细胞身份的重编程对于各种人类疾病的细胞替代疗法具有巨大的潜力，包括神经系统疾病，在这种疾病中，单个细胞丢失，人们希望用完整的、重编程的细胞替换这些细胞。

DESCRIPTION (provided by applicant): The ability of transcription factors to reprogram the identity of cells is usually very limited and hampers our ability to generate cells types for various different applications. In this grant proposal, entitled "Generating neurons through cellular reprogramming", we propose to conduct genetic screens in the nematode C. elegans that will identify factors that normally act to prevent the ability of transcription factors to reprogram cellular identities. In preliminary work, two such "reprogramming brakes" were identified. Further genetic screens may reveal more of these reprogramming inhibitors and help us better understand the plasticity of cellular, and specifically neuronal identity. This grant proposal makes specific use of the C. elegans model system as a gene discovery tool. PUBLIC HEALTH RELEVANCE: This research proposal studies the molecular mechanisms that underlie the reprogramming of the identity of individual cells. Conceptually, the reprogramming of cellular identity has enormous potential for cell replacement therapies of various human diseases, including neurological diseases, in which individual cells are lost and in which one wishes to replace those cells with intact, reprogrammed cells.