States of G₀ and the proliferation-quiescence decision in cells, tissues and during development

While cellular proliferation is fundamental to the development of all multicellular organisms, the slowing or stopping of proliferation at the right places and times is equally important for proper tissue and organ development. The non-cycling state of cellular quiescence or "G₀" is relatively understudied compared to proliferation, given its prevalence in nature. It may seem that actively proliferating cells undergo a series of dynamic events, while quiescent cells are in a passive, static state. However, studies over the last 10-15 years suggest that quiescence may be more dynamic than previously thought and must also be actively regulated and maintained. This review focuses on recent advances in understanding quiescence or G₀ and in particular, on observations about the proliferation-quiescence decision in cell lines, in tissues and during development. We also discuss novel, advanced molecular tools that are likely to enable the field to address outstanding, unresolved questions about cellular quiescence and its regulation.