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

基本信息

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
项目类别：
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

项目摘要

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然而，人们对肾细胞的整合、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 的目标是解决问题。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建立在我们已经建立的基础上，描述人类肾脏的细胞和分子组织。 HuBMAP 表征管道，我们将汇集高成像质谱、多路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 测序每种模式都经过专门选择以实现构建。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、邻近区域和整个器官）和分子类别（例如代谢物、脂质、蛋白质和 RNA）。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在目标 1 中，我们将继续我们的分子询问流程和 HuBMAP 研究人员生成的数据。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创建人类肾脏代表性分子图谱的采集计划目标 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 Aim 3 的重点提出了 2D 和 3D 多模态成像策略。以及对手术切除标本的深入多组学分析的开发。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。 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。