Generating neurons through cellular reprogramming

描述(申请人提供)：转录因子重新编程细胞身份的能力通常是非常有限的，并阻碍我们为各种不同的应用产生细胞类型的能力。在这项题为“通过细胞重编程产生神经元”的拨款提案中，我们建议在线虫中进行基因筛选，以识别正常情况下阻止转录因子重新编程细胞身份的因素。在初步工作中，确定了两个这样的“重新编程刹车”。进一步的基因筛查可能会揭示更多这样的重新编程抑制物，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。这项拨款提案特别使用线虫模型系统作为基因发现工具。 与公共健康相关：这项研究计划研究个体细胞身份重新编程的分子机制。从概念上讲，细胞身份的重新编程对于包括神经系统疾病在内的各种人类疾病的细胞替代疗法具有巨大的潜力，在这些疾病中，单个细胞丢失，人们希望用完整的、重新编程的细胞来取代这些细胞。

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.