Washington University Senescence Tissue Mapping Center (WU-SN-TMC)

华盛顿大学衰老组织图谱中心 (WU-SN-TMC)

• 批准号: 10685417
• 负责人: FENG CHEN
• 金额: $ 150万
• 依托单位: WASHINGTON UNIVERSITY
• 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/10685417
• 关键词: 3-Dimensional; Age; Animal Model; Atlases; Automobile Driving; Basic Science; Bioinformatics; Biological Assay; Biological Markers; Bone Marrow; Breast; Cell Aging; Cell Culture Techniques; Cell Cycle Arrest; Cell model; Cell physiology; Cells; Cellular biology; Clinical Research; Clinical Sciences; Clinical Trials Design; Collaborations; Collection; Colon; Comparative Study; Computer Models; Coupled; Data; Data Analyses; Data Coordinating Center; Disease; Evaluation; Funding; Genetic Transcription; Genome; Genomics; Goals; Heterogeneity; Homeostasis; Human; Image; Imaging technology; Informatics; Infrastructure; Institution; Investigation; Knowledge; Light; Liver; Longevity; Maps; Medicine; Methods; Microscopy; Operative Surgical Procedures; Organ; Pathology; Patients; Phenotype; Physicians; Physiological; Positioning Attribute; Production; Proteomics; Ramp; Reporting; Reproducibility; Research; Research Personnel; Resolution; Resource Sharing; Sampling; Science; Scientist; Signal Pathway; Skin; Small Intestines; Specific qualifier value; Standardization; Stomach; Structure; Technology; Time; Tissues; Translational Research; United States National Institutes of Health; Universities; Validation; Visualization; Washington; Work; age related; animal model selection; biobank; cellular imaging; clinical translation; computerized tools; data sharing; experience; high resolution imaging; human disease; human tissue; imaging platform; insight; medical schools; member; molecular imaging; novel; precision medicine; programs; proteogenomics; senescence; sex; single cell sequencing; single molecule; synergism; technology development; timeline; tissue mapping; transcriptomics

Overall Project Summary/Abstract Cellular senescence has been characterized as a state of irreversible cell-cycle arrest coupled with a secretory program that can profoundly impact the tissue microenvironment. Our current understanding of senescence is largely based on cell culture and model-based studies. Research on the relevant signaling pathways and mechanisms underlying cellular senescence across human tissues over time is lacking. Our ability to leverage recent advances in omics and molecular imaging technologies enables us to investigate the transcriptional changes and secretory features driving and/or associated with senescence at higher depths and resolution than ever before. Here, we propose to develop the Washington University Senescence Tissue Mapping Center (WU-SN-TMC) within the NIH Senescence Network (SenNet). Our WU-SN-TMC will develop cellular senescence atlases using 500 human samples from four essential tissue types: bone marrow, breast, colon, and liver. We will first optimize our omics and imaging technologies and platforms for capturing, detecting, characterizing, and visualizing senescent cells; develop computational tools and models for accurate identification of senescent cells and markers; construct breast, bone marrow, colon, and liver senescence atlases in spatial and temporal contexts; and assess the landscape and heterogeneity of senescence. With these initial atlases, we will further characterize, validate, and define cellular senescence phenotypes and biomarkers using perturbation methods and investigate the interactions between senescent cells and the senescence-associated microenvironment. Finally, we will work with other SenNet centers to build comprehensive, major organ/tissue senescence atlases by integrated and comparative studies of all SenNet data across tissue types, time, sex, age, and ancestry groups. As a member of the SenNet program, WU-SN- TMC will employ state-of-the-art omics and imaging technologies, including bulk proteogenomics, single cell sequencing, spatial transcriptomics, CODEX molecular imaging, 3D light sheet microscopy plus expansion technologies that are likely to mature over the funding period, such as single molecule sequencing, to generate high-resolution, multi-parameter biomarkers and maps of cellular senescence in the four tissue types selected. We have the established infrastructure and expertise to successfully conduct this work, including high quality biospecimen collection, omics and imaging data production, experimental confirmation and validation, and high throughput, standardized, and reproducible data analysis. In conclusion, we will work closely with other SenNet centers and the Consortium Organization and Data Coordination Center (CODCC), to generate comprehensive atlases across major human tissue types under various physiological conditions, including changes across the human lifespan.

总体项目总结/摘要 细胞衰老被描述为一种不可逆的细胞周期停滞状态，并伴随着分泌 可以深刻影响组织微环境的程序。我们目前对衰老的认识是 主要基于细胞培养和基于模型的研究。相关信号通路研究 随着时间的推移，人体组织细胞衰老的机制尚不清楚。我们的杠杆能力 组学和分子成像技术的最新进展使我们能够研究转录 在更高深度和分辨率下驱动和/或与衰老相关的变化和分泌特征 比以往任何时候都更重要。在这里，我们建议建立华盛顿大学衰老组织图谱中心 NIH 衰老网络 (SenNet) 内的 (WU-SN-TMC)。我们的 WU-SN-TMC 将开发蜂窝 使用来自四种基本组织类型的 500 个人体样本绘制衰老图谱：骨髓、乳腺、 结肠和肝脏。我们将首先优化我们的组学和成像技术以及捕获平台， 检测、表征和可视化衰老细胞；开发计算工具和模型以准确 识别衰老细胞和标记；构建乳房、骨髓、结肠和肝脏衰老 空间和时间背景下的地图集；并评估衰老的景观和异质性。和 通过这些初始图谱，我们将进一步表征、验证和定义细胞衰老表型， 使用微扰方法研究生物标志物并研究衰老细胞与衰老细胞之间的相互作用 衰老相关的微环境。最后，我们将与其他SenNet中心合作建立 通过对所有 SenNet 的综合和比较研究，获得全面的主要器官/组织衰老图谱 跨组织类型、时间、性别、年龄和血统群体的数据。作为 SenNet 计划的成员，WU-SN- TMC 将采用最先进的组学和成像技术，包括批量蛋白质组学、单细胞 测序、空间转录组学、CODEX 分子成像、3D 光片显微镜加扩展 在资助期内可能成熟的技术，例如单分子测序，以产​​生 所选四种组织类型的高分辨率、多参数生物标志物和细胞衰老图。 我们拥有成功开展这项工作的既定基础设施和专业知识，包括高质量 生物样本采集、组学和成像数据生成、实验确认和验证以及高 吞吐量、标准化和可重复的数据分析。总之，我们将与其他 SenNet 密切合作 中心和联盟组织和数据协调中心（CODCC），以生成全面的 不同生理条件下主要人体组织类型的图谱，包括整个组织的变化 人类的寿命。