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

项目摘要/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，目的是识别衰老的强大生物标记物，并由此建立组织- 细胞、微环境和分泌体水平的特定图谱。BAC将产生高分辨率， 高含量、高通量的生物分子数据，以生成六年内细胞衰老的全面地图 两个小鼠模型系统中的初级小鼠组织--一大群多样性杂交(DO)小鼠 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) 开发和应用管道以生成无偏、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、高含量的组织表型鉴定流水线 并将其应用于400只DO小鼠的队列中，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 小鼠品系，以全面分析从老年小鼠中分离的衰老细胞。一旦完成，这个项目将 已经从对照组的六个小鼠组织中生成了多尺度、多维的衰老细胞图 和感觉剂处理的组织，这些信息将是优化和指导未来感觉剂的关键 对人体试验的干预。

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.