Cell Size Regulation in Mammalian Cells

Abstract

The regulation of cell growth and proliferation is fundamental for animal development and homeostasis but the mechanisms that coordinate cell growth with cell cycle progression are poorly understood. One possibility is that “cell‑size checkpoints” act to delay division until cells have achieved a minimal size or mass however, the existence of such checkpoints in mammalian cells is controversial. In this study we provide further evidence against the operation of a size checkpoint in mammalian cells. We show that primary mammalian cells proliferate at a rate that is independent of cell size or cell mass and that cell size is “set” by the balance of extracellular growth factors and mitogens. Moreover, we show that commonly used culture conditions stimulate cell growth much more than cell cycle progression resulting in cells that proliferate at sizes 300–500% larger than their in vivo counterparts. This has profound effects on cell behavior.The regulation of cell growth and proliferation is fundamental for animal development and homeostasis but the mechanisms that coordinate cell growth with cell cycle progression are poorly understood. One possibility is that “cell‑size checkpoints” act to delay division until cells have achieved a minimal size or mass however, the existence of such checkpoints in mammalian cells is controversial. In this study we provide further evidence against the operation of a size checkpoint in mammalian cells. We show that primary mammalian cells proliferate at a rate that is independent of cell size or cell mass and that cell size is “set” by the balance of extracellular growth factors and mitogens. Moreover, we show that commonly used culture conditions stimulate cell growth much more than cell cycle progression resulting in cells that proliferate at sizes 300–500% larger than their in vivo counterparts. This has profound effects on cell behavior.