A Multi-scale Atlas of Senescence in Diverse Tissue Types

总体情况：项目总结 确定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缺口 田野。哥伦比亚大学衰老组织测绘中心(CUSTMAP)独一无二地准备 通过创建成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，建立在长期和已建立的协作基础上 哥伦比亚大学欧文医学中心(CUIMC)、爱丁堡大学、纽约大学 (纽约大学)和纽约基因组中心(NYGC)。利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管道，CUSTMAP将产生三个- 易受年龄相关退变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 (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 在中枢神经系统(CNS)和皮肤组织中进行的成像(4I)实验，允许 在太空中以单细胞分辨率进行史无前例的全基因组分子表征。CUSTMAP是 围绕三个科学核心以及一个行政核心来支持这些综合努力。 通过BiOspecimen Core(BIO)表征和收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， 从而在单细胞分辨率下绘制出人体组织中衰老细胞及其影响的详细图谱。这个 CUSTMAP的成功取决于能否从健康的个体获得持续的人体组织供应 在整个生命周期内。CUSTMAP调查人员可以接触到身体样本和预期的组织 从CUIMC的本地资源以及通过已建立的合作关系收集。我们独特的地理位置 曼哈顿上城的地理位置使得从当地种族丰富的患者群体中获取组织成为可能 和种族多样性。因此，CUSTMAP是从这些不同的组织中获得高质量组织的唯一准备 并应用尖端的多组学方法建立完整的衰老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 人类细胞衰老与年龄相关变化的新的分子、细胞和区域相关性 纸巾。CUSTMAP工作流程和计算工具很容易推广到其他组织类型和 可以高效地与Sennet联盟共享并在其上部署。

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.