Minnesota Tissue Mapping Center for Senescent Cells

明尼苏达衰老细胞组织绘图中心

基本信息

批准号：
10682547
负责人：
Constantin F. Aliferis
金额：
$ 170万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10682547
关键词：
Adipose tissue Aging Alzheimer&apos s Disease Architecture Archives Atlases Attenuated Bioinformatics Biological Biological Process Biology Birth Cell Aging Cells Cellular biology Chairperson Chromatin Clinic Clinical Clinical Trials Collaborations Collection Communication Communities Complex Computational Biology Consent DNA Methylation Data Data Analyses Data Coordinating Center Data Discovery Data Science Detection Disease Electronic Health Record Embryonic Development Equipment Excision FAIR principles Formalin Gene Expression Generations Genetic Genome Genomics Goals Human Human Resources Human Subject Research Hypertension Image Immune system Immunology Informatics Infrastructure Institution Insulin International Knowledge Leadership Learning Link Liver Longevity Maps Measurement Measures Metadata Minnesota Modeling Molecular Multiplexed Ion Beam Imaging Mus Muscle Operative Surgical Procedures Organ Organism Ovarian Tissue Paraffin Embedding Pathologic Pathologist Pathology Patients Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phenotype Physiological Physiology Plasma Play Procedures Process Proteomics Public Health Informatics Quality Control Research Research Personnel Role Sampling Skeletal Muscle Technology Therapeutic Tissue Procurements Tissues Tumor Suppression United States National Institutes of Health Universities Visualization Work age related aged aging population biomarker identification data management data modeling data sharing experience extracellular frailty healthy aging human tissue improved nano-string novel therapeutic intervention pharmacologic phenotypic biomarker quality assurance research study resilience response senescence single cell technology stressor subcutaneous success synergism therapeutic target tissue mapping transcriptomics vastus lateralis virtual wound healing

项目摘要

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.

项目概要众所周知，衰老细胞 (SnC) 在衰老和许多与年龄相关的疾病中发挥着因果作用。它们还有助于伤口愈合和组织重塑，生理和病理作用都是相关的。 SnCs 的分泌组及其与免疫系统的复杂相互作用，被认为发挥着重要作用我们对 SnCs 的了解大部分来自小鼠，因为它具有清除 SnCs 的重要作用。已明确证明，通过基因或药物手段去除衰老或患病生物体中的 SnC 减少虚弱；提高力量、耐力和恢复能力；并减轻各种与年龄相关的疾病；这种针对常见的基本衰老过程的新治疗方法。许多疾病——而不是药物治疗特定疾病的扰动（例如低胰岛素或高血压）——可以然而，对于人类中的 SnC，我们还需要了解很多。安全有效地部署此类方法该项目旨在建立一个组织绘图中心。明尼苏达大学 (MN TMC) 将为 SenNet 联盟做出贡献，该联盟打算建立一个 4D 图集健康衰老的多个人体器官中的 SnCs MN TMC 建议重点关注脂肪（网膜和脂肪）。皮下组织）、骨骼肌（股外侧肌）、肝脏和卵巢组织。此选择基于 MN TMC。这些器官的生物学、细胞生物学和免疫学方面的专业知识；以及 MN TMC 及其行政核心将由在这些器官的单细胞技术方面的经验领导。在 SnC 和计算生物学/健康信息学方面具有互补专业知识的 PI。将由 UMN 外科主席和一位经验丰富的病理学家领导。由 SnC 专家和 UMN 空间基因组学领导者分子病理学家领导。 Core 将由三位生物信息学家领导，他们在建模、单细胞和空间组学分析方面拥有专业知识，将患者电子健康记录与组学数据相结合所提议的 MN TMC 的一个独特功能是：整个工作流程将安置在现有的基础设施/核心中：来自 CTSI 和 BioNet，它们管理人类受试者研究、组织采购、注释和分发/存储，直至基因组/ 蛋白质组学/成像核心，以及健康信息学研究所的数据管理和多重分析。关键人员包括所有这些 UMN 组件的领导。这种方法提供了无与伦比的稳定性。我们的分析流程和到位的质量控制和保证机制的第二个独特之处。拟议的 MN TMC 是我们对福尔马林固定石蜡进行空间转录组学和蛋白质组学的能力嵌入式生物样本，可以分析最稳定的生物样本和几乎任何存档的生物样本总体而言，MN TMC 的目标是为人类 SnCs 的 4D 图谱做出重大贡献，与 NIH 和其他 TMC 密切合作，制定并遵守 SenNet 联盟制定的标准。