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.

整体项目摘要/摘要