The purpose for the Cellular Senescence Network (SenNet) is to catalyze the development of a framework for mapping cellular senescence and its associated secretory phenotype at high resolution, to provide atlases of cellular senescence in multiple tissues and under diverse conditions, including early development, and across the lifespan.
The goal of the Cellular Senescence Network (SenNet) is to identify and functionally characterize the heterogeneity of senescent cells across multiple tissues in human health, and lifespan at single-cell resolution.
The deliverables will provide a sound platform to develop approaches for the betterment of human health. This will be achieved by:
– generating multimodal atlases that characterize the heterogeneity and spatial distribution of senescent cells in health and across the lifespan, at single cell resolution;
– determining reliable biomarker panels to identify senescent cells as well as their secretory properties in vivo and/or ex vivo;
– establishing the next generation of tools, and experimental and computational model systems amenable to perturbations, necessary to construct high resolution atlases of cellular senescence;
– establishing parameters for regulating senescence, both at the level of inducers and their removal through senolytics, immune therapy, or other means;
– dramatically improving imaging tools to identify and validate senescence at the cellular, tissue and whole-body levels.
There are three research initiatives that comprise the program:
- Tissue Mapping Centers (TMCs)- These Centers will generate extensive data from high-content, high-throughput imaging, omics, and other technologies as appropriate, to build, benchmark, standardize, and validate senescent cell maps at high resolution. Tissue Mapping Centers will be expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through data generation, integration, analysis, and interpretation.
- Technology Development Projects– These projects will establish proof of principle and validation of the next generation of tools, techniques and methods that can be implemented by the consortium for studying cellular senescence and their Senescence Associated Secretory Phenotype (SASP). The goal is to promote the development of novel, innovative technologies to study cellular senescence in model systems and/or human tissues.
- Consortium Organization and Data Coordination Center (CODCC)- The CODCC will serve as an organizational hub for the consortium. It will collect, store, curate, and disseminate all data, metadata, analyses and visualization tools, computational models, and completed tissue maps generated by the SenNet consortium. It will develop controlled access workspaces for consortium working groups, and an outfacing portal, the Senescence Atlas, to the scientific community for access to the tools, technologies, and tissue-level atlases developed by the TMCs and Technology Hubs.
The SenNet effort builds upon and extends existing single cell tissue mapping efforts including the Human Tumor Atlas Network, Human Biomolecular Atlas Program, and Human Cell Atlas. Together with the SenNet program, these efforts will continue to generate important resources for the scientific community that will inform future research and, ultimately, clinical decision-making. While the current RFA is focused only on human tissues, the goal of the SenNet is to construct atlases of cellular senescence across multiple tissues, in response to multiple inducers and modifiers in both mice and humans. The SenNet will be comprised of Tissue Mapping Centers (this RFA), solicited under RFA-RM-21-008) and Technology Development Projects (solicited under RFA-RM-21-009), and a Consortium Organization and Data Coordination Center (CODCC, solicited under RFA-RM-21-010).