A Multi-scale Atlas of Senescence in Diverse Tissue Types

不同组织类型衰老的多尺度图谱

基本信息

批准号：
10385184
负责人：
Angela M Christiano
金额：
$ 271.2万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
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/10385184
关键词：
3-Dimensional Address Adult Affect Age Aging Atlases Automobile Driving Autopsy Biological Biology of Aging Blood Brain Cell Aging Cell Nucleus Cells Cerebrospinal Fluid Clinical Collaborations Communities Data Data Analyses Data Collection Data Science Dermatologic Dermatology Ensure Environment Fostering Gene Expression Profile Genome Genomics Geographic Locations Goals Heterogeneity Human Image Indirect Immunofluorescence Individual Knowledge Leadership Longevity Maps Medical center Modality Molecular Molecular Profiling Neuraxis Neurology New York Pathologic Pathology Phase Phenotype Population Heterogeneity Procedures Process Proteomics Protocols documentation Reproductive Biology Research Research Personnel Resolution Resources Sampling Skin Skin Tissue Small Nuclear RNA Spinal Cord Structure Techniques Technology Tissue Banks Tissue Procurements Tissue Sample Tissues Universities Visualization Work age related base biobank cell type computerized tools data resource ethnic diversity experience experimental study genome-wide genomic data human tissue innovation molecular phenotype multidisciplinary multiple omics novel novel marker patient population prospective protein expression racial diversity regenerative senescence success synergism tool transcriptome sequencing transcriptomics

项目摘要

OVERALL: PROJECT SUMMARY Defining the molecular and cellular heterogeneity underlying senescent cell states is a critical knowledge gap in the field. The Columbia University Senescence Tissue Mapping (CUSTMAP) Center is uniquely poised to address this gap by creating a multi-scale atlas of senescence in diverse tissue types across the adult human lifespan. CUSTMAP is a highly collaborative effort that builds upon long-standing and established collaborations between Columbia University Irving Medical Center (CUIMC), The University of Edinburgh, New York University (NYU), and the New York Genome Center (NYGC). Using state-of-the-art spatial genomics technologies and leveraging our established experimental workflows and analytical pipelines, CUSTMAP will generate three- dimensional maps of senescent cells in tissues with vulnerability to age-related degenerative processes: the central nervous system (brain and spinal cord) and the skin. We will perform spatially resolved transcriptomics (ST), single-nucleus RNA-sequencing, and multiplexed proteomics using iterative indirect immunofluorescence imaging (4i) experiments in central nervous system (CNS) and skin tissues across the human lifespan, allowing for unprecedented genome-wide molecular characterization at single-cell resolution in space. CUSTMAP is structured around three scientific Cores, as well as an Administrative Core to support these integrated efforts. Human tissue samples characterized and collected through the Biospecimen Core (BIO) will be analyzed using the tools and techniques developed through the Biological Analysis Core (BAC) and Data Analysis Core (DAC), leading to detailed maps of senescent cells and their effects in human tissues at single-cell resolution. The success of CUSTMAP is predicated on access to a continuous supply of human tissues from healthy individuals across the lifespan. CUSTMAP investigators have access to post-mortem samples and prospective tissue collection from local resources at CUIMC as well as through established collaborations. Our unique geographic location in Upper Manhattan enables tissue acquisition from a local population of patients that is rich in racial and ethnic diversity. Thus, CUSTMAP is uniquely poised to obtain high-quality tissue from these diverse populations and apply cutting-edge multiomic approaches to build integrated 3D molecular atlases of senescent cells in CNS and skin tissues. Our approach provides a unique platform for driving transformative discoveries of novel molecular, cellular and regional correlates of age-related changes in cellular senescence in human tissues. The CUSTMAP workflow and computational tools are readily generalizable to other tissue types and can be efficiently shared with and deployed across the SenNet Consortium.

总体而言：项目概要定义衰老细胞状态背后的分子和细胞异质性是一个关键的知识差距领域。哥伦比亚大学衰老组织图谱 (CUSTMAP) 中心具有独特的优势通过创建成年人不同组织类型的多尺度衰老图谱来解决这一差距寿命。 CUSTMAP 是一项高度协作的工作，建立在长期和既定的合作基础上哥伦比亚大学欧文医学中心 (CUIMC)、爱丁堡大学、纽约大学之间（纽约大学）和纽约基因组中心（NYGC）。使用最先进的空间基因组学技术和利用我们已建立的实验工作流程和分析流程，CUSTMAP 将生成三个：易受年龄相关退化过程影响的组织中衰老细胞的维度图：中枢神经系统（大脑和脊髓）和皮肤。我们将进行空间分辨转录组学 (ST)、单核 RNA 测序和使用迭代间接免疫荧光的多重蛋白质组学在整个人类生命周期中对中枢神经系统 (CNS) 和皮肤组织进行成像 (4i) 实验，使得在太空中以单细胞分辨率进行前所未有的全基因组分子表征。定制地图是围绕三个科学核心以及一个支持这些综合努力的行政核心构建。通过生物样本核心 (BIO) 表征和收集的人体组织样本将使用以下方法进行分析通过生物分析核心 (BAC) 和数据分析核心 (DAC) 开发的工具和技术，以单细胞分辨率绘制衰老细胞及其对人体组织影响的详细图谱。这 CUSTMAP 的成功取决于能够持续供应来自健康个体的人体组织贯穿整个生命周期。 CUSTMAP 研究人员可以获得尸检样本和前瞻性组织从 CUIMC 的当地资源以及通过既定的合作收集。我们独特的地理位于曼哈顿上城的位置使得能够从当地具有丰富种族背景的患者群体中获取组织和种族多样性。因此，CUSTMAP 具有独特的优势，能够从这些多样化的组织中获取高质量的组织。人口并应用尖端的多组学方法来构建衰老的综合 3D 分子图谱中枢神经系统和皮肤组织中的细胞。我们的方法为推动变革性发现提供了一个独特的平台人类细胞衰老与年龄相关变化的新分子、细胞和区域相关性组织。 CUSTMAP 工作流程和计算工具很容易推广到其他组织类型和可以在 SenNet 联盟中高效共享和部署。