Postdoctoral Fellow Stanford University Stanford, CA, United States
Abstract: The heterogeneity in stem cell cycle underlies many aspects of tissue dynamics, including turnover rate and clonogenicity. A large body of work has identified the intricate and multitudinous ways that extracellular information regulate stem cell behavior. However, the quantitative nature of cell cycle decisions are still not well-understood, especially in vivo. Here, we show that a cell size homeostasis mechanism, first identified in yeast and subsequently in cell cultures, autonomously governs the decision to enter S phase in epidermal stem cells. Cell-extrinsic factors like variation in the cellular microenvironment affects cell growth rates but not the autonomous coupling of cell size to the G1/S transition. We confirm this finding using laser ablation experiments to perturb the cellular microenvironment, and show that the coupling between cell size and the G1/S transition remains invariant despite upregulation of cellular growth rates. Lastly, we show that this cell-intrinsic coupling between cell size and cell cycle progression is conserved to cycling cells in the intestinal epithelium lineage, as well as cycling osteoblast cells in the zebrafish scale. Our work overhauls long-standing models of cell cycle regulation within complex metazoan tissues and reinforces the importance of cell-intrinsic size control as a critical factor regulating cell division in vivo.
