Investigation of senescent cell heterogeneity by CITE-seq analysis of the surfaceome

National Institute On Aging

Investigators

Abstract

Cellular senescence is a key mechanism that could has been targeted to delay aging and ameliorate age-related diseases. However, the heterogeneity of senescence cells poses significant challenges to identify specific senescence programs and design effective therapeutic strategies. To address these challenges, we propose a comprehensive approach to characterize senescence heterogeneity by identifying novel surface-associated senescence proteins and tracking their development throughout senescence progression. This characterization will be markedly enhanced using CITE-seq technology, which enables the classification of senescent cell clusters based on surface proteins to reveal distinct subpopulations. By integrating transcriptomic analysis with cell surface proteins, we will define the molecular pathways driving senescence heterogeneity. Finally, we will validate these senescence clusters using FACS and establish new experimental models based on purified senescent subpopulations. Successful completion of these aims will provide a high-resolution map of senescence heterogeneity, enhance our ability to define senescent cell subpopulations (senotypes), and pave the way for novel therapeutic strategies to intervene in age-related diseases.