Vanderbilt University Biomolecular Multimodal Imaging Center for 3-Dimensional Mapping of the Human Kidney

范德比尔特大学生物分子多模态成像中心进行人体肾脏 3 维绘图

• 批准号: 10701832
• 负责人: Jeffrey M Spraggins
• 金额: $ 163.65万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701832
• 关键词: 3-Dimensional; Address; Affect; Anatomy; Antibodies; Atlases; Biological Assay; Biological Markers; Blood capillaries; Cell Separation; Cells; Characteristics; Clinical; Collection; Cytometry; Data; Data Analyses; Disease; Dissociation; Distal; Duct (organ) structure; Elements; Emerging Technologies; Excision; Exclusion; Filtration; Fluorescence; Gene Expression Profiling; Goals; Heterogeneity; Histologic; Homeostasis; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Immunofluorescence Microscopy; Individual; Kidney; Knowledge; Link; Lipids; Location; Lymphatic; Maps; Methods; Microscopy; Mission; Modality; Molecular; Molecular Analysis; Molecular Profiling; Morphology; Multimodal Imaging; Neighborhoods; Nephrons; Operative Surgical Procedures; Organ; Preparation; Property; Proteins; Proteomics; Protocols documentation; Quality Control; RNA; Research Personnel; Sampling; Sodium Chloride; Source; Specimen; Stains; Standardization; Structure; Tissue Banks; Tissue Sample; Tissues; Tubular formation; Universities; Water; analysis pipeline; assay development; automated segmentation; biobank; blood pressure control; cell type; data management; experimental study; extracellular; human tissue; imaging facilities; insight; interstitial; kidney cell; mass spectrometric imaging; molecular imaging; multimodality; multiple omics; programs; scale up; single-cell RNA sequencing; surgery material; tissue mapping; transcriptomics

PROJECT SUMMARY – Kidney OSP. The overall structure and anatomical relationships among different cell types within the human kidney are well understood, and experimental studies have defined the molecular and functional characteristics of individual kidney cell types. However, remarkably little is known about the integration, interactions, and molecular cross- talk between the different cellular compartments in normal kidneys. The goal of the Kidney OSP is to address this limitation in current knowledge by developing a fully integrated, multimodal molecular imaging pipeline to characterize the cellular and molecular organization of the human kidney. Building on our already established HuBMAP characterization pipeline, we will bring together imaging mass spectrometry, highly multiplexed immunofluorescence microscopy, autofluorescence microscopy, stained microscopy, spatial transcriptomics, spatial proteomics, and single-cell RNA-seq. Each modality was specifically chosen to enable the construction of a kidney molecular atlas that spans a wide range of spatial scales (e.g., single cells, functional tissue units, neighborhoods, and whole organs) and molecular classes (e.g., metabolites, lipids, proteins, and RNAs). The result will be a comprehensive molecular atlas of the human kidney that will be fully compatible with other molecular interrogation pipelines and data generated by HuBMAP researchers. In Aim 1 we will continue our kidney tissue collection and management protocols that build on our established kidney biobanks and tissue acquisition programs to create a representative molecular atlas of the human kidney. Aim 2 establishes clinical and histological standards and metrics that will be used to determine the suitability of samples that can be entered into the analytical pipeline. The focus of Aim 3 puts forth a strategy for 2-D and 3-D multimodal imaging and deep multi-omic analysis of the human kidney. Assay development on surgical resection specimens will be applied to whole organs using non-transplantable donor kidneys to construct 3-D molecular atlases. Finally, Aim 4 will scale up the kidney-specific characterization pipeline to generate representative 3-D molecular atlases from multiple, intact human kidneys.

项目摘要 – 肾脏 OSP。 人肾内不同细胞类型之间的整体结构和解剖关系良好 理解，实验研究已经定义了个体的分子和功能特征 肾细胞类型。然而，人们对整合、相互作用和分子交叉知之甚少。 正常肾脏中不同细胞区室之间的对话。肾脏 OSP 的目标是解决 通过开发完全集成的多模式分子成像管道来克服当前知识的局限性 表征人类肾脏的细胞和分子组织。建立在我们已经建立的基础上 HuBMAP 表征管道，我们将汇集成像质谱、高度复用 免疫荧光显微镜、自发荧光显微镜、染色显微镜、空间转录组学、 空间蛋白质组学和单细胞 RNA 测序。每种方式都经过专门选择，以实现施工 跨越广泛空间尺度的肾脏分子图谱（例如，单细胞、功能组织单位、 邻域和整个器官）和分子类别（例如代谢物、脂质、蛋白质和 RNA）。这 结果将是一个全面的人类肾脏分子图谱，该图谱将与其他肾脏图谱完全兼容 HuBMAP 研究人员生成的分子询问管道和数据。在目标 1 中，我们将继续我们的 基于我们已建立的肾脏生物库和组织的肾脏组织收集和管理方案 采集计划以创建人类肾脏的代表性分子图谱。目标 2 建立临床 以及组织学标准和指标，用于确定样品的适用性 进入分析管道。 Aim 3的重点提出了2D和3D多模态成像策略 以及人类肾脏的深入多组学分析。手术切除标本的检测开发将 使用不可移植的供体肾脏应用于整个器官以构建 3D 分子图谱。最后，瞄准 4 将扩大肾脏特异性表征流程以生成代表性的 3D 分子图谱 来自多个完整的人类肾脏。