A Multi-scale Atlas of Senescence in Diverse Tissue Types

不同组织类型衰老的多尺度图谱

• 批准号: 10683316
• 负责人: Angela M Christiano
• 金额: $ 262.77万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 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/10683316
• 关键词: 3-Dimensional; Address; Adult; Affect; Age; Aging; Atlases; Automobile Driving; Autopsy; Biological; Biology of Aging; Blood; Brain; Cell Aging; Cells; Central Nervous System; 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; 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; Spinal Cord; Structure; Techniques; Technology; Tissue Banks; Tissue Procurements; Tissue Sample; Tissues; Universities; Visualization; Work; age related; biobank; cell type; computerized tools; data integration; ethnic diversity; experience; experimental study; genome-wide; genomic data; human tissue; innovation; molecular phenotype; multi-scale atlas; multidisciplinary; multiple omics; neuropathology; novel; novel marker; patient population; prospective; protein expression; racial diversity; regenerative; senescence; single nucleus RNA-sequencing; success; synergism; tissue mapping; tool; transcriptomics; 3-Dimensional; Address; Adult; Affect; Age; Aging; Atlases; Automobile Driving; Autopsy; Biological; Biology of Aging; Blood; Brain; Cell Aging; Cells; Central Nervous System; 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; 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; Spinal Cord; Structure; Techniques; Technology; Tissue Banks; Tissue Procurements; Tissue Sample; Tissues; Universities; Visualization; Work; age related; biobank; cell type; computerized tools; data integration; ethnic diversity; experience; experimental study; genome-wide; genomic data; human tissue; innovation; molecular phenotype; multi-scale atlas; multidisciplinary; multiple omics; neuropathology; novel; novel marker; patient population; prospective; protein expression; racial diversity; regenerative; senescence; single nucleus RNA-sequencing; success; synergism; tissue mapping; tool; transcriptomics

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：项目摘要 定义分子和细胞异质性潜在的衰老细胞状态是一个关键的知识差距 领域。哥伦比亚大学衰老组织图（Custmap）中心是独特的准备 通过在成年人的各种组织类型中创建一个多尺度衰老地图，以解决这一差距 寿命。 CustMap是一项高度协作的努力，它基于长期和建立的合作 纽约大学爱丁堡大学哥伦比亚大学欧文医学中心（CUIMC）之间 （NYU）和纽约基因组中心（NYGC）。使用最先进的空间基因组技术和 利用我们既定的实验工作流程和分析管道，CustMap将产生三个 易于年龄相关的退化过程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。我们将执行空间分辨的转录组学 使用迭代间接免疫荧光（ST），单核RNA序列和多重蛋白质组学 中枢神经系统（CNS）和人类寿命的皮肤组织的成像（4i）实验，允许 对于空间中单细胞分辨率下的空前基因组分子表征。 Custmap是 在三个科学核心和行政核心围绕这些综合努力的构造。 通过生物晶体核心（BIO）进行表征和收集的人体组织样品将使用 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， 在单细胞分辨率下导致衰老细胞的详细地图及其在人体组织中的影响。这 Custmap的成功取决于获得健康个体的人类组织的连续供应 整个生命周期。 Custmap调查人员可以使用验尸样本和前瞻性组织 从Cuimc的本地资源以及既定的合作中收集。我们独特的地理 曼哈顿上部的位置可从当地的患者群体中获取组织 和种族多样性。因此，Custmap独特地准备从这些多样的 种群并采用尖端的多构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独特的平台 人类细胞衰老中与年龄相关的新分子，细胞和区域相关性 组织。 CustMap工作流程和计算工具很容易被推广到其他组织类型，并且 可以有效地与Sennet财团共享和部署。