The Jackson Laboratory Senescence Tissue Mapping Center (JAX-Sen TMC) - Biological Analysis Core

杰克逊实验室衰老组织绘图中心 (JAX-Sen TMC) - 生物分析核心

• 批准号: 10683389
• 负责人: Paul Robson
• 金额: $ 125.97万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683389
• 关键词: 3-Dimensional; Adipose tissue; Adult; Age; Age Months; Animals; Antibodies; Area; Atlases; Biological; Biological Markers; Biological Models; Biology; Cell Aging; Cell Nucleus; Cell Separation; Cells; Cellular biology; Collaborations; Data; Data Analyses; Data Set; Development; Dimensions; Ensure; Epitopes; Fluorescent in Situ Hybridization; Funding; Future; Genes; Genetic Variation; Goals; Heart; Hematoxylin and Eosin Staining Method; Human; Hypothalamic structure; Image; Individual; Intervention; Kidney; Label; Laboratories; Leadership; Maps; Mass Spectrum Analysis; Measurement; Modeling; Molecular; Molecular Profiling; Mus; Pancreas; Phenotype; Placenta; Proteomics; RLK5-associated protein phosphatase; Reporter; Research Personnel; Resolution; Resources; Shock; Sorting; Stains; Technology; The Jackson Laboratory; Time; Tissue Microarray; Tissues; Transcript; aged; cell type; cohort; epigenetic profiling; genetic association; genetic signature; imaging platform; innovation; lipidomics; mass spectrometric imaging; metabolomics; mouse model; new technology; response; senescence; single molecule; single nucleus RNA-sequencing; single-cell RNA sequencing; success; tissue mapping; tissue reconstruction; transcriptome sequencing; transcriptomics

PROJECT SUMMARY/ABSTRACT BIOLOGICAL ANALYSIS CORE The primary objective of the Biological Analysis Core (BAC) of the JAX-Sen mouse Tissue Mapping Center (TMC) is to provide high resolution state-of-the-art molecular, cellular, and tissue-level characterization of mouse tissues for the purpose of identifying robust biomarkers of senescence and, from this, build tissue- specific atlases at the cellular, microenvironment, and secretome levels. The BAC will generate high resolution, high content, high-throughput biomolecular data to generate comprehensive maps of cellular senescence in six primary mouse tissues, across two mouse model systems - a large cohort of Diversity Outbred (DO) mice representing genetic diversity and the required C57BL/6 strain. To achieve these goals, the BAC will 1) develop and apply a pipeline to generate unbiased, high-quality, high-resolution, and high-throughput datasets to discover biomarkers of senescence, 2) develop a high-throughput, high-content tissue phenotyping pipeline and apply this to a cohort of 400 DO mice, 3) generate high biomolecular content, multi-parameter spatial measurements on 2D serial sections to enable 3D tissue reconstruction, and 4) leverage p16/p21 reporter mouse lines to comprehensively profile senescent cells sorted from aged mice. Once complete, this project will have generated multi-scale, multi-dimensional maps of senescence cells within six mouse tissues from control and senolytics treated tissues, information that will be critical to optimize and guide future senolytic interventions in human trials.

项目摘要/摘要生物分析核心 JAX-SEN小鼠组织映射中心的生物分析核心（BAC）的主要目标 （TMC）是提供高分辨率的最先进的分子，细胞和组织水平的表征 小鼠组织是为了鉴定衰老的鲁棒生物标志物，并从中构建组织 - 细胞，微环境和分材水平的特定图谱。 BAC将产生高分辨率， 高含量，高通量生物分子数据，以生成六个细胞衰老的综合图 跨两个小鼠模型系统的原代小鼠组织 - 大量多样性（DO）小鼠队列 代表遗传多样性和所需的C57BL/6菌株。为了实现这些目标，BAC将1） 开发和应用管道来生成公正，高质量，高分辨率和高通量数据集 要发现衰老的生物标志物，2）开发高通量，高核组织表型管道 并将其应用于400只小鼠的队列，3）产生高的生物分子含量，多参数空间 对2D串行部分的测量以实现3D组织重建，4）利用P16/P21报告器 小鼠线以全面介绍从老年小鼠分类的衰老细胞。完成后，这个项目将 从对照中产生了六个小鼠组织中衰老细胞的多尺度的多维图 和塞溶剂治疗的组织，对于优化和指导未来的鼻溶剂至关重要的信息 人类试验的干预措施。