XenCAT: Xenopus Single Cell Atlas

项目摘要 由于人类疾病的一场革命，人类疾病的遗传原因正在迅速被识别 人类基因组学。然而，向更深层次理解的进展需要进一步的分析。 潜在的发育、细胞和分子机制，以及 建立预测性疾病模型以测试治疗方案。归根结底，基因不会 函数；它们在空间和时间上分组在多个嵌套级别上， 最显著的功能单位是单个细胞。在细胞内观察生物系统 级别提供了一个前所未有的机会来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。这些上下文中的许多都保留在 进化，偏离进化会产生重要的创新，但也会导致 畸形和疾病。因此，正在建立一份人类细胞图谱，希望它 将构成这一单细胞观点的核心。在模型生物中的并行工作将是至关重要的， 细胞图谱目前正在构建中，例如在老鼠和斑马鱼中。来自格登的 通过表征驱动细胞的细胞周期蛋白，发现核重编程 根据最近关于细胞间信号传递的许多发现，非洲爪哇仍然处于 生物医学研究作为一种独特的模式。我们建议为此建立一个单一细胞图谱 重要的模式系统，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。 它将是对其他新兴非洲爪哇工具的重要补充，例如CRISPR编辑的突变体 品系，这些品系最容易表现出发育和成体功能的特点-- 细胞水平。此外，两栖类胚胎细胞的巨大细胞尺寸已经使单细胞 非洲爪哇可能存在蛋白质组学，远远领先于其他生物；因此，非洲爪哇是天然的 引领向单细胞蛋白质组学转变的选择。总体而言，该项目将 增强用于研究人类疾病机制的关键动物模型并开放 为其他研究所的许多已经得到支持的NIH项目开辟新的天地，这些项目侧重于 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.