XenCAT: Xenopus Single Cell Atlas

项目摘要 人类疾病的遗传原因正在迅速确定，这要归功于人类基因组学的革命。 基因组学然而，要想取得更深入的了解，还需要进一步分析 潜在的发育，细胞和分子机制，以及建立 预测疾病模型来测试治疗方案。最后，基因不能在 隔离;他们在空间和时间上分组在多个嵌套的水平，最显着的 功能单位是单个细胞。在细胞水平上观察生物系统提供了一个 前所未有的机会来定义功能模块化和组合的相互作用， 各种生理环境中的基因。许多这样的背景在进化中是保守的， 偏离这些原则会产生重要的创新，但也会导致畸形， 疾病因此，正在建立一个人类细胞图谱，希望它将成为这一研究的核心。 单细胞视角在模式生物中的平行工作将是至关重要的， 目前在小鼠和斑马鱼中构建。从古尔登发现核能 重编程，通过表征驱动细胞周期的细胞周期蛋白，到许多最近的 尽管非洲爪蟾在细胞间信号传递方面有了新的发现，但它仍然处于生物医学研究的前沿， 独一无二的模型我们建议为这个重要的模型系统建立一个单细胞图谱， 将提高非洲爪蟾已有的独特方法的价值， 与包括人类在内的其他实验系统进行通信。这将是一个关键的补充， 到其他新兴的爪蟾工具，如CRISPR编辑的突变系，这可能是最容易 其特征在于单细胞水平的发育和成年功能。此外，大细胞 两栖动物胚胎细胞的大小已经使非洲爪蟾的单细胞蛋白质组学成为可能， 远远领先于其他生物;因此，爪蟾是带头转变的自然选择 走向单细胞蛋白质组学。总的来说，这个项目将加强一个关键的动物模型， 人类疾病机制的研究，并为许多已经得到支持的 NIH在其他研究所的项目，重点是特定的器官系统和疾病。

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.