Researchers have observed that a small number of cells in the human body lose their ability to divide, but remain active cells. There are many unanswered questions about these “senescent cells,” including how they contribute to both chronic diseases of aging and healthy functions like wound healing. The NIH Common Fund’s Cellular Senescence Network (SenNet) is identifying and characterizing senescent cells to construct “atlases” that will show where different types of senescent cells are located within human and mouse tissues. SenNet researchers rely on multiple methods to characterize the cells, including spatial transcriptomics, which pairs imaging and genetic sequencing techniques to measure gene activity in precise locations of a tissue sample. Location plays an important role for senescent cells because they often release molecules that affect neighboring cells. However, there is a need for computational methods that can use spatial transcriptomics data to better understand unique cell features resulting from the cell’s location in the tissue. Fortunately, the NIH Common Fund’s 4D Nucleome (4DN) program has spent significant time advancing technology that combines imaging and genetic sequencing, like spatial transcriptomics, in its effort to study how the shape and arrangement of chromatin in the cell influences gene activity and consequently human health.

A research team led by Dr. Jian Ma, a member of both the SenNet and 4DN programs, developed a computational method called SPICEMIX that can analyze spatial transcriptomics data to understand cell identities in tissues containing multiple cell types, like those being collected in SenNet. Using models of the cortex region of the mouse brain, SPICEMIX matched or outperformed existing methods in identifying cell types using information about gene activity and location. SPICEMIX could identify cell types specific to a certain layer of tissue or found sparsely distributed across multiple tissue layers. These cell types are more difficult to identify using existing methods. Development of new tools like SPICEMIX brings the field closer to understanding how, when, where, and why senescent cells form in the body and how they may play a role in chronic diseases of aging.

Reference:
SPICEMIX enables integrative single-cell spatial modeling of cell identity. Chidester B, Zhou T, Alam S, Ma J. Nature Genetics. 2023 Jan;55(1):78-88. doi: 10.1038/s41588-022-01256-z. Epub 2023 Jan 9.

Cellular senescence plays an important role in human health. During senescence, certain cells stop dividing and produce chemicals that affect neighboring cells. Senescent cells accumulate as we age and there is promise in using senotherapeutics, or drugs that target cellular senescence, to treat diseases of aging. However, there is a lack of knowledge about how to identify senescent cells in the body and how to describe differences in senescent cells across tissues. Because no single lab is capable of the comprehensive approach needed to fully characterize these cells, the NIH Common Fund’s Cellular Senescence Network (SenNet) consortium was assembled with expertise across multiple tissues and technologies.

In a marker paper, members of the SenNet consortium and NIH working group lay out their plan for characterizing and providing an atlas of senescent cells in humans and mice. Several other deliverables were discussed, including novel tools, technologies, and data sets, validated biomarkers, a clear and comprehensive definition of senescent cells in various tissues, and collaborative efforts with other existing cell mapping programs to enable data integration and knowledge sharing. The planned technologies, methods, and data formats are also discussed to make the biomedical research community aware of what SenNet plans to make available in the future. To keep up-to-date on the consortium’s progress, visit their website at sennetconsortium.org.

Reference:
NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health. SenNet Consortium. Nature Aging. 2022 Dec 20. doi:10.1038/s43587-022-00326-5.

Many of the cells in our body undergo numerous cycles of dividing from one cell into two. However, a small number of cells stop this process of dividing and become “senescent.” Despite their important roles in health, disease, and aging, there are still many unanswered questions about how, when, why, and where senescent cells form. The Common Fund’s Cellular Senescence Network (SenNet) began its work to comprehensively identify and characterize the differences in senescent cells across the body and lifespan in the fall of 2021. To begin this important work, the program established a network made up of three key components: Human Tissue Mapping Centers, Technology Development and Application (TDA) projects focused on future use in human tissues, and a Consortium Organization and Data Coordination Center (CODCC) to act as the organizational hub. The initial goals of SenNet focused on mapping senescent cells in humans, but it was recognized early on by the program that studies in animal models could enable researchers to ask questions that would otherwise be too difficult to answer in humans. Identifying the differences and similarities in cellular senescence between mice and humans may also allow researchers to better design animal studies that yield insight into human health.

Recognizing the importance of understanding senescent cells in mice and developing tools for characterizing these cells specifically in animal models, SenNet has broadened its mission by funding five Murine Tissue Mapping Centers as well as two TDA projects focused on future use in mouse tissues. An additional three TDA projects focused on future use in human tissues were also awarded to further enhance the range of technologies used within the Network. The CODCC will continue to collect, store, and curate the Network’s data to deliver human and mouse atlases of senescence to the scientific community, which will catalyze research on the role of senescent cells in human health and how to manipulate senescent cells to improve health. Visit the Network’s website or subscribe to its mailing list to stay up-to-date on SenNet news!

Read more about the new projects on the Funded Research webpage.