XenCAT: Xenopus Single Cell Atlas

XenCAT：非洲爪蟾单细胞图谱

• 批准号: 10807246
• 负责人: Marko E Horb
• 金额: $ 24.88万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10807246
• 关键词: Adopted; Adult; Amphibia; Animal Model; Atlases; Benchmarking; Biological Metamorphosis; Biological Models; Biomedical Research; Brain; Cell Cycle; Cell Nucleus; Cell Size; Cells; Cellular biology; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communication; Communities; Complement; Cyclins; Data; Data Set; Destinations; Development; Disease; Disease model; Dissociation; Embryo; Embryology; Embryonic Development; Evolution; Extracellular Matrix; Funding; Gene Expression Profiling; Genes; Genetic; Genetic Transcription; Heart; Human; Immune system; Individual; Infrastructure; Investigation; Kidney; Learning; Left; Link; Methods; Modeling; Molecular; Mus; Natural regeneration; Neurobiology; Nuclear; Organ; Organism; Organogenesis; Physiological; Physiology; Procedures; Process; Proteins; Proteomics; Protocols documentation; Publishing; Research; Research Personnel; Research Project Grants; Resolution; Rest; Sampling; Science; Signal Transduction; Specialist; Specific qualifier value; System; Time; Tissue atlas; Tissues; United States National Institutes of Health; Work; XenBase; Xenopus; Zebrafish; biological systems; blastomere structure; body system; cell type; combinatorial; data sharing; embryo cell; experience; experimental study; gastrulation; gene interaction; human disease; human genomics; innovation; insight; malformation; model organism; mutant; nuclear reprogramming; single cell analysis; therapeutic evaluation; tool; transcriptomics

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.

项目摘要 由于一场革命 人类基因组学。但是，要深入了解需要进一步分析 潜在的发育，细胞和分子机制以及 建立预测疾病模型以测试治疗选择。最终，基因不 隔离功能；它们经常在多个嵌套级别上分组 最显着的功能单元是单个单元。在细胞上观察生物系统 Level提供了一个前所未有的机会来定义功能模块化和组合 基因在各种物理背景下的相互作用。这些背景中的许多是保守的 进化，出发产生重要创新但也导致 畸形和疾病。彼此之间，正在建造人类细胞地图集，希望它 将构成这种单细胞观点的核心。模型生物中的平行工作至关重要， 目前正在构建细胞图谱，例如在鼠标和斑马鱼中。来自古顿的 通过表征驱动细胞的细胞周期蛋白来发现核重编程 循环，对于细胞之间的许多最新发现，爪蟾仍然处于 生物医学研究，是一种独特的模型。我们建议为此建立一个单元图集 重要的模型系统将增强已经可用的唯一方法的价值 在Xenopus中，并允许与包括人类在内的其他实验系统进行有效的沟通。 这将是对其他新兴的Xenopus工具的关键补充，例如CRISPR编辑的突变体 线，最容易在单个发育和成人功能中表征 细胞水平。此外，两栖细胞的较大细胞大小已经使单细胞成为单细胞 爪蟾可能的蛋白质组学可能领先于其他生物；因此，爪蟾是自然的 率先向单细胞蛋白质组学转移的选择。总体而言，这个项目将 增强关键动物模型，以研究人类疾病机制并开放 许多已经支持其他机构的NIH项目的新视野，这些项目专注于特定 器官系统和疾病。