Gel-based Optical-isolation Single-Cell 3D Spatial Multiomics

基于凝胶的光隔离单细胞 3D 空间多组学

• 批准号: 10473394
• 负责人: Xiaoyu Shi
• 金额: $ 137.83万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 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 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10473394
• 关键词: 3-Dimensional; Address; Benchmarking; Brain; Cell Separation; Cell physiology; Cells; DNA; Development; Disease; Environment; Gel; Goals; Health; Human; Human body; Image; Label; Link; Maps; Methods; Microbe; Microscopy; Mission; Neurons; Optics; Pattern; Process; Proteins; Proteomics; Publishing; RNA; Resolution; Skin; Structure; Technology; Thinness; Tissues; United States National Institutes of Health; base; cell type; design; healing; host microbiome; innovation; insight; multiple omics; novel; protein profiling; single cell analysis; tool; transcriptomics; tumor; tumorigenesis; wound; wound healing

ABSTRACT Proper functioning of the human body relies on the organization of cells in 3D space. A cell’s function and fate are determined by its biomolecule composition and its 3D environment. The spatially identification of proteins, RNAs, and DNAs in a tissue thus provides a powerful map to decipher how cells build tissues and become diseased. Through the use of single-cell omics, it’s been possible to reveal rare cell types that benchmark development, oncogenesis, and brain functions. However, the cell isolation process in single-cell analysis unavoidably causes loss of spatial information. To obtain spatial information, spatial transcriptomics based on imaging or sequencing have emerged to give insight into the heterogeneous expression patterns in tumors, brain, and wound tissues. Unfortunately, most spatial transcriptomics methods can only examine thin tissue sections, and are incompatible with proteomics. To address these drawbacks, the goal of the project is to develop a conceptually novel 3D spatial multiomics technology featuring gel-based optical isolation (GO3D). The proposed GO3D technology is distinct from all current spatial omics, and will enable the profiling of proteins, RNAs, and DNAs of whole-mount tissues with subcellular resolution, high coverage and high throughput, simultaneously. This innovative design is based on the gel-based label-retention expansion microscopy (LR- ExM) that the PI published recently. GO3D will drastically transform our understanding of many critical biomedical questions, which we lack of tools to address currently. For example, how are cells in a highly dynamic skin migrate in 3D to heal wounds? How do specialized neurons build brain? And where do microbes interact with what cell types in gut?

抽象的 人体的正确功能依赖于3D空间中细胞的组织。单元的功能 命运由其生物分子组成及其3D环境决定。在空间上识别 因此，组织中的蛋白质，RNA和DNA提供了一个强大的图表，以破译细胞如何构建组织和 被解散。通过使用单细胞OMIC，可以揭示稀有细胞类型 基准开发，肿瘤发生和大脑功能。但是，单细胞中的细胞隔离过程 不可避免地会导致空间信息的丢失。为了获得空间信息，空间转录组学 基于成像或测序已出现，以深入了解异质表达模式 肿瘤，大脑和伤口组织。不幸的是，大多数空间转录组方法只能检查薄 组织切片，与蛋白质组学不兼容。为了解决这些缺点，该项目的目标是 开发一种概念性小说3D空间多素技术，具有基于凝胶的光学隔离（GO3D）。 拟议的GO3D技术与所有当前的空间幻义不同，将使蛋白质分析， RNA，以及具有亚细胞分辨率，高覆盖范围和高吞吐量的全置组织的DNA 这种创新的设计基于基于凝胶的标签 - 持续扩展显微镜（LR- exm）最近发布的PI。 GO3D将大大改变我们对许多关键生物医学的理解 问题，我们缺乏目前无法解决的工具。例如，高度动态皮肤中的细胞如何 以3D迁移以治愈伤口？专业神经元如何造成大脑？微生物与哪里相互作用 肠道中哪些细胞类型？