权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Bioanalysis Core

生物分析核心

基本信息

批准号：
10553046
负责人：
PETER D. ADAMS
金额：
$ 186.35万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10553046
关键词：
Ablation Address Age Aging Architecture Atlases Biological Biological Assay Bone Marrow Brain Breast Cell Aging Cells Cellular Assay Characteristics Chromatin Collaborations Colon DNA Methylation Data Data Analyses Data Set Disease Epigenetic Process Evaluation Exhibits Female Foundations Functional disorder Future Gene Expression Genes Genetic Goals Heterogeneity Histone Deacetylase Histone Deacetylase Inhibitor Human Imaging technology In Situ Individual Inflammatory Knowledge Link Liver Longevity Maps Measurement Molecular Molecular Profiling Mouse Strains Mus Neighborhoods Organ Pharmacology Phenotype Population Research Resolution Technology Tissue atlas Tissues Vorinostat Work drinking water epigenome epigenomics genetic approach histone modification innovation male multiple omics protein biomarkers senescence telomere tissue mapping tool transcriptome transcriptomics whole genome

项目摘要

PROJECT SUMMARY Cellular senescence, characterized by stable proliferation arrest and secretion of pro-inflammatory factors, is not only a hallmark of aging, but also a key contributor to age-associated diseases in humans. As the US population is aging, there is an added urgency to gain a better understanding of cellular senescence in different tissues over the lifespan. Unfortunately, we still lack the knowledge to unambiguously define senescence at the molecular and cellular levels, due to its heterogeneous phenotypes. To address this major gap in knowledge, we propose to establish a tissue mapping center that focuses on the identification and characterization of senescent cells in healthy male and female mouse brain, bone marrow, breast, colon and liver. Our research strategy builds on recent advances in single cell epigenomics technologies that our team developed and the knowledge that senescent cells exhibit characteristic changes in the chromatin landscapes, histone modifications and expression of marker genes of cellular senescence. We will deploy cutting-edge single cell in situ and tissue dissociative multi-omic tools that have been well established in our center to produce comprehensive single cell resolution maps of the transcriptome and epigenome in male and female mouse brain, bone marrow, breast, colon and liver, and to provide qualitative and quantitative spatial maps of the normal burden of senescent cells in these vital organs, across the lifespan of two mouse strains. We will rigorously validate the newly defined senescent cell populations using pharmacologic and genetic approaches to eradicate senescent cells or suppress their inflammatory phenotype, and orthogonal state-of-the-art and conventional assays for cellular senescence. We will generate whole genome single cell DNA methylation data to link our spatial atlas to measurement of epigenetic age, a candidate predictor of beneficial versus detrimental effects of senescent cells. We expect that comprehensive single cell atlases of epigenome and transcriptome will enable us to identify and characterize cellular senescence in different tissue contexts and during aging. We expect that the planned research will provide a reference for future studies that seek to characterize and target senescent cells associated with or preceding disease in brain, bone marrow, breast, colon and liver.

项目总结