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: 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
• 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

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：项目总结