Minnesota Tissue Mapping Center for Senescent Cells

项目摘要 衰老细胞(SNC)在衰老和许多与年龄相关的疾病中起着因果作用。然而， 它们还有助于伤口愈合和组织重塑。生理和病理作用都是联系在一起的 SNC的分泌体及其与免疫系统的复杂相互作用，这被认为起到了 在清算SNC方面发挥重要作用。我们所了解到的关于SNCs的大部分知识都来自于它具有 已清楚地证明，在衰老或患病的生物体中，SNCs的遗传或药物移除 减少虚弱；提高力量、耐力和韧性；减轻各种与年龄有关的疾病 包括阿尔茨海默氏症。这一新的治疗方法针对常见的基本衰老过程 许多疾病--而不是针对特定疾病的干扰(例如，低胰岛素或高血压)--可能 对我们老龄化的人口产生了巨大的影响。然而，对人类的SNC还有很多需要了解的地方 安全有效地部署这种方法。该项目旨在建立一个组织测绘中心在 明尼苏达大学(MN TMC)向Sennet财团捐款，该财团打算建立一个4D地图集 健康衰老的多个人体器官中的SNCs。MN TMC建议将重点放在脂肪(大网膜和 皮下)、骨骼肌(股外侧肌)、肝脏和卵巢组织。此选择基于MN TMC 在这些器官的生物学、细胞生物学和免疫学方面的专门知识；研究这些器官中的SNCs；以及 在这些器官中使用单细胞技术的经验。MN TMC及其行政核心将由以下人员领导 在SNCS和计算生物学/卫生信息学方面具有互补专业知识的PIS。Biosecimen核心 将由UMN外科主席和一位有造诣的病理学家领导。生物分析的核心意志 由北卡罗来纳大学的一位专家和一位在密歇根大学领导空间基因组学的分子病理学家领导。数据分析 CORE将由三名在建模、单细胞和空间组学分析方面拥有专业知识的生物信息学家领导，以及 将患者电子健康记录与组学数据相结合。拟议的MN TMC的一个独特之处是 整个工作流程将驻留在现有基础架构/核心中：来自CTSI和Bionet，它们管理 人类受试者研究、组织获取、注释和分发/存储，到基因组/ 蛋白质组学/成像核心，以及卫生信息学研究所，用于数据管理和多路传输。 关键人员包括所有这些UMN组成部分的领导。这种方法提供了无与伦比的稳定性 我们的分析流水线和就地质量控制和保证机制。的第二个独特功能 建议的MN TMC是我们在福尔马林固定的石蜡上执行空间转录和蛋白质组学的能力 嵌入式生物标记物，能够分析最稳定的生物标记物和几乎所有存档的生物标记物 材料。总体而言，MN TMC的目标是为人类SNC的4D地图集做出重大贡献， 与NIH和其他TMC密切合作，制定并遵守SENet联盟制定的标准。

Project Summary Senescent cells (SnCs) are known to play a causal role in aging and numerous age-related diseases. However, they also contribute to wound healing and tissue remodeling. Both physiological and pathological roles are linked to the secretome of SnCs and their complex interaction with the immune system, which is thought to play an important role in clearing SnCs. Most of what we have learned about SnCs is derived from mice where it has been clearly demonstrated that genetic or pharmacologic removal of SnCs in aged or diseased organisms reduces frailty; improves strength, endurance, and resilience; and attenuates a variety of age-related diseases including Alzheimer’s. This novel approach of therapeutically targeting a fundamental aging process common to many diseases – rather than drugging disease-specific perturbations (e.g., low insulin or hypertension) – could have a tremendous impact on our aging population. However, much needs to be learned about SnCs in humans to deploy such approaches safely and effectively. This project aims to establish a Tissue Mapping Center at the University of Minnesota (MN TMC) to contribute to the SenNet Consortium, which intends to build a 4D atlas of SnCs in multiple human organs with healthy aging. MN TMC proposes to focus on adipose (omental and subcutaneous), skeletal muscle (Vastus lateralis), liver, and ovarian tissue. This selection is based on MN TMC’s expertise in the biology, cell biology, and immunology of these organs; in studying SnCs in these organs; and experience with single cell technologies in these organs. The MN TMC and its Administrative Core will be led by PIs with complementary expertise in SnCs and computational biology/health informatics. The Biospecimen Core will be led by the UMN Chairman of Surgery and an accomplished pathologist. The Biological Analysis Core will be led by an expert in SnC and a molecular pathologist leading spatial genomics at UMN. The Data Analysis Core will be led by three bioinformaticians with expertise in modeling, single cell, and spatial-omics analysis, and blending patient electronic health records with -omics data. A unique feature of the proposed MN TMC is that the entire workflow will be housed within existing infrastructure/cores: from CTSI and BioNet, which manage human subjects research, tissue procurement, annotation, and distribution/storage, to the genomic/ proteomics/imaging cores, along with the Institute of Health Informatics for data management and multiplexing. Key personnel include leadership of all of these UMN components. This approach provides unequaled stability of our analytical pipeline and in-place quality control and assurance mechanisms. A second unique feature of the proposed MN TMC is our ability to perform spatial transcriptomics and proteomics on formalin-fixed paraffin embedded biospecimens, which enables analysis of the most stable biospecimens and virtually any archived material. Overall, the goal of the MN TMC is to make a significant contribution to the 4D atlas of human SnCs, working closely with NIH and other TMCs to develop and adhere to standards created by the SenNet Consortium.