A Multi-scale Atlas of Senescence in Diverse Tissue Types

总体：项目摘要 定义衰老细胞状态下的分子和细胞异质性是一个关键的知识缺口， 外地哥伦比亚大学衰老组织绘图（CUSTMAP）中心是独一无二的， 通过在成年人的不同组织类型中创建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 (NYU)和纽约基因组中心（NYGC）。利用最先进的空间基因组学技术， 利用我们建立的实验工作流程和分析管道，CUSTMAP将产生三个- 易受年龄相关退行性过程影响的组织中衰老细胞的三维图谱： 中枢神经系统（脑和脊髓）和皮肤。我们将用空间分辨转录组学 (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（4 i）实验， 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。CUSTMAP是 该中心围绕三个科学核心以及一个行政核心构建，以支持这些综合努力。 通过生物样本核心（BIO）表征和采集的人体组织样本将使用 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， 从而以单细胞分辨率绘制出衰老细胞及其在人体组织中的作用的详细图谱。的 CUSTMAP的成功取决于从健康个体获得持续的人体组织供应 在整个生命周期中。CUSTMAP研究人员可以获得死后样本和预期组织 从CUIMC的当地资源以及通过建立合作收集。我们独特的地理位置 位于上曼哈顿的位置使得能够从具有丰富种族背景的当地患者群体获得组织。 和种族多样性。因此，CUSTMAP是独一无二的，以获得高品质的组织，从这些不同的 人口和应用尖端的多组学方法来建立综合的3D分子图谱的衰老 CNS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 新的分子，细胞和区域相关的年龄相关的变化在细胞衰老在人类 组织中CUSTMAP工作流程和计算工具易于推广到其他组织类型， 可以在SenNet Consortium之间高效共享和部署。

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.