EAGER: New insights into the biology of cell transdifferentiation

EAGER：细胞转分化生物学的新见解

• 批准号: 1936565
• 负责人: Maria Pia Miglietta
• 金额: $ 29.43万
• 依托单位: Texas A&M University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1936565&HistoricalAwards=false
• 关键词: EAGER; New; insights; into; biology

The ultimate goal of regenerative research is to replace damaged cells in response to injuries and aging. Transdifferentiation (or cell reprogramming), a process through which a mature somatic cell transforms into a new type of mature somatic cell, can achieve this goal. The mechanisms by which cells spontaneously (in vivo) leave a differentiated state to become a new lineage are poorly understood. This is due to the difficulties in inducing transdifferentiation in live model systems. A new promising approach comes from the cnidarian Turritopsis dohrnii. Most animals reproduce, age, and die. T. dohrnii has escaped this fate. When faced with unfavorable circumstances, the jellyfish of T. dohrnii avoid death by reverting to a younger life cycle stage, the polyp. During the life cycle reversal, which covers a time span of about 24 hours, cell transdifferentiation occurs. These characteristics make T. dohrnii a potential new system for in vivo research on the molecular mechanisms of cell stability and transdifferentiation. This project will produce genomic tools and assess the potential of T. dohrnii as a system for the study of in vivo cellular differentiation. The research has three objectives: 1) Produce transcriptome assembly and annotation of T. dohrnii. 2) Produce a hybrid draft genome assembly and annotation of T. dohrnii. 3) Conduct differential gene expression analyses of life cycle stages of T. dohrnii. The genomic tools (draft genome and transcriptome assembly) will be crucial steps toward facilitating the development of genome editing tools. The differential gene expression analyses will provide insight on the specific genes that are associated with the mechanisms of cellular transdifferentiation that occur during the reverse development of T. dohrnii. This project supports outreach activities and the creation of a portal that will contain information, up to date research, useful links to scientific literature, pictures, and a high-definition video of T. dohrnii's life cycle reversal. With numerous unscientific and inaccurate websites on "the immortal jellyfish" these activities aim to populate the Internet with reliable information and visual products on T. dohrnii.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

再生研究的最终目标是响应损伤和衰老而替代受损细胞。转分化（或细胞重编程），这是一个成熟的体细胞转化为新型成熟的体细胞细胞的过程，可以实现此目标。细胞自发（体内）留下差异化状态以成为新谱系的机制知之甚少。这是由于在实时模型系统中诱导跨分化的困难。一种新的有前途的方法来自Cnidarian Turritopsis dohrnii。大多数动物会繁殖，年龄和死亡。 T. dohrnii逃脱了这种命运。当面对不利的情况时，T. dohrnii的水母避免了死亡，恢复到年轻的生命周期阶段，即息肉。在生命周期逆转中，覆盖约24小时的时间跨度，会发生细胞转分解。这些特征使T. dohrnii成为有关细胞稳定性和转分化分子机制的体内研究的潜在新系统。该项目将产生基因组工具，并评估T. dohrnii作为研究体内细胞分化的系统的潜力。该研究具有三个目标：1）产生T. dohrnii的转录组组装和注释。 2）产生混合基因组组装和T. dohrnii的注释。 3）进行T. dohrnii生命周期阶段的差异基因表达分析。基因组工具（基因组和转录组组装草案）将是促进基因组编辑工具开发的关键步骤。差异基因表达分析将提供有关特定基因与在T. dohrnii反向发育过程中发生的细胞转分化机制相关的特定基因的见解。该项目支持外展活动和创建门户网站，该门户将包含信息，最新的研究，与科学文献，图片的有用链接以及T. dohrnii的生命周期逆转的高清视频。这些活动旨在通过T. dohrnii上的可靠信息和视觉产品填充互联网的许多不科学和不准确的网站。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估来通过评估来获得支持的，并审查了更广泛的影响。