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: 10552967
• 负责人: Paul Robson
• 金额: $ 82.87万
• 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/10552967
• 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; Cells; Cellular biology; Collaborations; Data; Data Analyses; Data Set; Development; Ensure; Epitopes; Fluorescent in Situ Hybridization; Funding; Future; Genes; Genetic; 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; Stains; Technology; The Jackson Laboratory; Time; Tissue Microarray; Tissues; Transcript; aged; base; cell type; cohort; epigenetic profiling; genetic signature; imaging platform; innovation; lipidomics; mass spectrometric imaging; metabolomics; mouse model; new technology; response; senescence; single molecule; 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.

项目总结/抽象生物分析核心 JAX-Sen小鼠组织图谱中心生物分析核心（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，目的是鉴定衰老的稳健生物标志物，并由此构建组织- 在细胞、微环境和分泌组水平上的特异性图谱。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地图， 原代小鼠组织，在两个小鼠模型系统-一个大的群体的多样性远交（DO）小鼠 代表遗传多样性和所需的C57 BL/6菌株。为了实现这些目标，BAC将1） 开发和应用一个管道来生成无偏差、高质量、高分辨率和高吞吐量的数据集 为了发现衰老的生物标志物，2）开发高通量、高内容的组织表型分析管道 并将其应用于400只DO小鼠的队列，3）产生高生物分子含量、多参数空间 在2D连续切片上进行测量，以实现3D组织重建，以及4）利用p16/p21报告基因 小鼠品系，以全面分析从老年小鼠中分选的衰老细胞。一旦完成，该项目将 在对照组的六个小鼠组织中生成了衰老细胞的多尺度，多维图 和senolytics治疗的组织，信息将是至关重要的，以优化和指导未来senolytics 干预人体试验。