Biological Analysis Core

摘要-生物分析核心 细胞衰老是在正常组织中观察到的延长的且通常不可逆的生长停滞 发展虽然衰老对于组织重塑至关重要，但对于防止受损细胞中的恶性肿瘤， 在伤口愈合中，衰老细胞的异常积累与多种慢性炎症有关。 老年性疾病，如动脉粥样硬化、肺纤维化、神经变性等。衰老是 被看作是对各种压力的反应，包括端粒侵蚀，遗传毒性，营养剥夺，缺氧， 和线粒体功能障碍。生物分析核心与生物标本核心合作，将 通过集成和提供最先进的技术来调查， 分子、单细胞和整个组织水平的衰老。核心是由一个团队领导， 研究科学家成功地利用这些特定的平台与以前的和/或 目前的临床研究。与数据分析核心一起，生物分析核心将生成 多模态图谱，其表征衰老细胞在单个细胞中的异质性和空间分布 在包括肺、心脏、结肠、肌肉和皮肤在内的各种组织中以及在 发育包括胎儿/婴儿、儿童（<18岁）、青年（<35岁）、中年（<55岁）和 老年人（>55岁）。为了支持该联盟，并提供一套必要的衰老地图， 组织，生物分析核心将利用高度标准化和/或正式的 经验证的测定平台。首先关注肺部组织，我们将系统地分析心脏，肌肉，皮肤 和结肠组织，以提供跨越所有上述定义的年龄组的衰老的丰富组织图。生物 分析核心有以下具体目标：1）提供高分辨率的最先进的分子，细胞， 以及生物样本的组织水平表征，目的是鉴定衰老的稳健生物标志物 并构建详细的组织图，2）收集和分析匹配的生物流体，包括血液、脑脊髓 液体，唾液和尿液，提供了多个衰老地图之间更广泛的相互联系， 组织和不同发育阶段，以及3）开发人源性基于微流体的液滴 来自各种组织的类器官以模拟适合于扰动的独特系统， 衰老干预药物。所有这些样本、衍生品和数据都将提供给整个 组织绘图中心联盟和我们的团队将致力于整合和优化数据的所有部分 生成管道，从组织收集和保存到数据生成、集成、分析， 解释。

ABSTRACT – Biological Analysis Core Cellular senescence is a prolonged and generally irreversible growth arrest observed in normal tissue development. While senescence is vital for tissue remodeling, for prevention of malignancy in damaged cells, and in wound healing, the aberrant accumulation of senescence cells is associated with multiple chronic diseases of aging such as atherosclerosis, pulmonary fibrosis, neurodegeneration and others. Senescence is seen as a response to various stressors including telomere erosion, genotoxicity, nutrient deprivation, hypoxia, and mitochondrial dysfunction. The Biological Analysis Core, in partnership with the Biospecimen Core, will be a critical resource for the SenNet proposal by integrating and delivering state-of-the-art technology to investigate senescence at the molecular, single-cell, and whole tissue level. The core is led by a team of highly accomplished research scientists who have successfully utilized these specific platforms in conjunction with previous and/or current clinical studies. Together with the Data Analysis Core, the Biological Analysis Core will generate multimodal atlases that characterize the heterogeneity and spatial distribution of senescent cells at single cell resolution in various tissues including lung, heart, colon, muscle, and skin and across different stages of development consisting of fetal/infant, pediatric (<18 years old), young adults (<35), middle adults (<55), and older adults (>55). To support the consortium and provide the requisite set of senescence maps across different tissues, Biological Analysis Core will utilize a comprehensive repertoire of highly standardized and/or formally validated assay platforms. With the initial focus on lung tissue, we will systematically profile heart, muscle, skin and colon tissues to provide rich tissue maps of senescence across all above-defined age groups. The Biological Analysis Core has the following Specific Aims: 1) to provide high resolution state-of-the-art molecular, cellular, and tissue-level characterization of biospecimens for the purpose of identifying robust biomarkers of senescence and constructing detailed tissue maps, 2) to collect and analyze matching biofluids including blood, cerebrospinal fluid, saliva, and urine, providing a broader interconnection between the senescence maps across multiple tissues and at varying developmental stages, and 3) to develop human-derived microfluidic-based droplet organoids from various tissues to model unique systems amenable to perturbations that test the efficacy of novel drugs for senescence intervention. All of these samples, derivatives, and data will be available to the entire Tissue Mapping Center consortium and our team will work to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation to data generation, integration, analysis, and interpretation.