Molecular Imaging Biomedical Resource Core

项目摘要/摘要-分子成像核心 分子成像核心的首要目标是在 对实验动物和人类来源肾组织的询问和分析。这个目标将是 通过实施以下具体目标来实现：1)向肾脏研究界提供 三项影响较大的服务：索引联合检测(CODEX)、大规模3D成像和组织细胞术 (3DTC)和空间转录学(ST)，以及2)提供分析支持，以确保分子的输出 成像可在技术内部和跨技术进行解释和集成，并且数据输出与 最佳做法，并与整个肾病界使用的细胞类型和状态定义协调一致。这个 可以单独提供技术以促进蛋白质组和转录信号的空间锚定， 或者在同一组织标本上一起提供。综合输出可以通过直接合作实现 连续截面上的配准或分析空间中的对齐。提供的分析支持将 允许调查人员测试假设并为细胞类型和状态注释创建通用框架 跨越多个NIDDK计划。总之，通过分子成像核心提供的技术将 允许研究人员定义、定位和量化：1)所有细胞群，2)3D内的细胞-细胞相互作用 邻域，3)形态变化和损伤区域，4)18,000个基因的表达 5)深免疫表型和损伤表型在空间上锚定。这样的输出提供了独特的 为肾脏社区提供强大的服务。这项拟议的研究意义重大，因为预计它将 帮助肾病界确定疾病进展的急需生物标记物，优化 临床前研究，并为广泛的肾脏开发特定和有针对性的治疗干预措施 疾病。

Project Summary/Abstract - Molecular Imaging Core The overarching goal of the Molecular Imaging Core is to provide full-service assistance in the interrogation and analysis of experimental animal and human-derived kidney tissue. This goal will be accomplished through the conduct of the following specific aims: 1) Provide the renal research community with three high impact services: Co-Detection by Indexing (CODEX), Large-scale 3D imaging and Tissue Cytometry (3DTC), and spatial transcriptomics (ST) and 2) Provide analytic support to ensure the outputs of molecular imaging are interpretable and integrated within and across technologies, and data outputs are consistent with best practices and are harmonized with cell-type and state definitions used across the renal community. The technologies can be offered individually to facilitate spatial anchoring of proteomic and transcriptomic signals, or offered together on the same tissue specimen. An integrated output can be accomplished by direct co- registration on consecutive sections or alignment in the analytical space. The analytical support provided will allow investigators to test hypotheses and create a common framework for cell type and state annotation across multiple NIDDK initiatives. Together, the technologies offered through the Molecular Imaging Core will allow investigators to define, localize, and quantify: 1) all cell populations, 2) cell-cell interactions within 3D neighborhoods, 3) morphological changes and injury regions, 4) the expression of 18,000 genes mapped over histopathology, and 5) deep immune and injury phenotypes anchored spatially. Such outputs provide a unique and powerful service to the renal community. The proposed research is significant, because it is expected to aid the renal community in identifying critically needed biomarkers of disease progression, optimizing preclinical studies, and developing specific and targeted therapeutic interventions for a wide range of kidney diseases.