Multiple transcription factors maintain the cellular quiescence

Quiescence is the counterpart to proliferation: a reversible, nondividing state. Many different types of cells can enter a quiescent state including single-celled bacteria and yeast and tissue-resident cells of multicellular organisms such as worms, mouse, and humans. In mammals, induction of quiescence in stem and differentiated cells is associated with widespread changes in gene expression patterns that coordinate the maintenance of quiescence hallmarks such as reversibility and repression of cell cycle genes. These patterns are mediated in part by the activity of transcription factors, but the structure of these TF networks is not well understood. Using a well-defined and physiologically relevant human fibroblast model of quiescence, we reconstruct these TF networks using genomic and computational methods. We find that the quiescence hallmarks are regulated by the activities of multiple TFs that may be repressive or activating. This is different from other cellular changes that require a small set of TFs. We discovered that Notch signaling pathway members including HES1 TF plays a role in protecting quiescent fibroblasts from irreversible states of senescence and differentiation. The results support an important role for the Notch pathway in ensuring the reversibility of the quiescent state. Finally, we find the quiescent state to be heterogenous and how these quiescence states are defined by specific TF networks is under investigation. Muscle Cell Biology, Pathophysiology, and Therapeutics T32 AR065972, Whitcome Fellowship, University of California Cancer Research Coordinating Committee This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.