XenCAT: Xenopus Single Cell Atlas

项目摘要 人类疾病的遗传原因正在迅速被确定，这要归功于一场革命。 人类基因组学然而，要想取得更深入的了解，还需要进一步的分析 潜在的发育，细胞和分子机制，以及 建立预测疾病模型以测试治疗方案。最终，基因不会 它们在空间和时间上按多个嵌套级别分组， 最显著的功能单位是单个细胞。在细胞中观察生物系统 级别提供了前所未有的机会，定义功能模块化和组合 基因在各种生理环境中的相互作用。这些背景中的许多在 进化，偏离它产生重要的创新，但也导致 畸形和疾病。因此，正在建立一个人类细胞图谱，希望它 将成为单细胞理论的核心。在模式生物中的平行工作将是至关重要的， 并且目前正在例如小鼠和斑马鱼中构建细胞图谱。从古尔登的 发现核重编程，通过表征驱动细胞的细胞周期蛋白 周期，许多最近发现的细胞之间的信号，非洲爪蟾仍然处于最前沿， 生物医学研究，作为一个独特的模式。我们建议为此建立一个单细胞图谱 一个重要的示范系统，将提高现有独特方法的价值 并允许与包括人类在内的其他实验系统进行有效通信。 它将成为其他新兴非洲爪蟾工具的重要补充，例如CRISPR编辑的突变体， 线，这可能是最容易的特点，在发展和成人的功能，在单一的- 细胞水平。此外，两栖动物胚胎细胞的大细胞尺寸已经使单细胞 蛋白质组学可能在非洲爪蟾，远远领先于其他生物;因此，非洲爪蟾是自然的 是引领单细胞蛋白质组学转变的首选。总体而言，该项目将 加强关键动物模型的研究人类疾病的机制和开放 新的视野，许多已经支持的NIH项目在其他研究所，重点是具体的 器官系统和疾病。

Project Summary The genetic causes of human diseases are rapidly being identified thanks to a revolution in human genomics. Progress toward a deeper understanding, however, requires further analysis of the underlying developmental, cellular and molecular mechanisms, as well as the establishment of predictive disease models to test therapeutic options. Ultimately, genes do not function in isolation; they are grouped spatially and temporally at multiple nested levels, the most salient functional unit being the single cell. Observing biological systems at the cellular level provides an unprecedented opportunity to define functional modularity and combinatorial interactions of genes in various physiological contexts. Many of these contexts are conserved in evolution, deviations from which produce important innovations but which also lead to malformations and disease. Accordingly, a Human Cell Atlas is being built with the hope that it will form a core of this single-cell perspective. Parallel work in model organisms will be crucial, and cell atlases are being constructed currently e.g. in mouse and zebrafish. From Gurdon’s discovery of nuclear reprogramming, through characterization of the cyclins that drive the cell cycle, to many recent discoveries on signaling among cells, Xenopus remains at the forefront of biomedical research, as a unique model. We propose to establish a Single Cell Atlas for this important model system which would enhance the value of the unique methods already available in Xenopus and allow effective communication to other experimental systems including human. It will be a critical complement to other emerging Xenopus tools, such as CRISPR-edited mutant lines, which could be most easily characterized in developmental and adult function at the single- cell level. Moreover, the large cell size of amphibian embryonic cells has already made single-cell proteomics possible in Xenopus, well ahead of other organisms; thus, Xenopus is the natural choice for spearheading the shift towards single-cell proteomics. Overall, this project will enhance a critical animal model for the investigation of human disease mechanisms and open new horizons for many already supported NIH projects in other Institutes that focus on specific organ systems and disease.