EAGER: New insights into the biology of cell transdifferentiation

再生研究的最终目标是替换受损细胞以应对损伤和衰老。转分化（或细胞重编程）是一种成熟体细胞转化为新型成熟体细胞的过程，可以实现这一目标。细胞自发地（在体内）离开分化状态成为新谱系的机制尚不清楚。这是由于在活体模型系统中诱导转分化的困难。一种新的有希望的方法来自刺胞动物杜氏灯塔。大多数动物繁殖、衰老和死亡。T. dohrnii逃脱了这种命运。当面对不利的环境时，T. dohrnii水母通过恢复到更年轻的生命周期阶段，即水螅体来避免死亡。在大约24小时的生命周期逆转过程中，细胞发生转分化。这些特点使杜氏弓形虫成为研究细胞稳定性和转分化分子机制的潜在新系统。该项目将开发基因组工具，并评估dohrnii作为体内细胞分化研究系统的潜力。本研究主要有三个目的：1)建立dohrnii的转录组组装和注释。2)制作dohrnii的杂交草图基因组组装和注释。3)对dohrnii虫生命周期阶段进行差异基因表达分析。基因组工具（草图基因组和转录组组装）将是促进基因组编辑工具发展的关键步骤。差异基因表达分析将提供与多氏弓形虫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一个门户网站，该网站将包含信息、最新研究、科学文献的有用链接、图片和关于T. dohrnii生命周期逆转的高清视频。有许多关于“不朽的水母”的不科学和不准确的网站，这些活动的目的是在互联网上普及关于T. dohrnii的可靠信息和视觉产品。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.