G0 phase

The G₀ phase describes a cellular state outside of the replicative cell cycle. Classically^[when?], cells were thought to enter G₀ primarily due to environmental factors, like nutrient deprivation, that limited the resources necessary for proliferation. Thus it was thought of as a resting phase. G₀ is now known to take different forms and occur for multiple reasons. For example, most adult neuronal cells, among the most metabolically active cells in the body, are fully differentiated and reside in a terminal G₀ phase. Neurons reside in this state, not because of stochastic or limited nutrient supply, but as a part of their developmental program.

G₀ was first suggested as a cell state based on early cell cycle studies. When the first studies defined the four phases of the cell cycle using radioactive labeling techniques, it was discovered that not all cells in a population proliferate at similar rates.^[1] A population's "growth fraction" – or the fraction of the population that was growing – was actively proliferating, but other cells existed in a non-proliferative state. Some of these non-proliferating cells could respond to extrinsic stimuli and proliferate by re-entering the cell cycle.^[2] Early contrasting views either considered non-proliferating cells to simply be in an extended G₁ phase or in a cell cycle phase distinct from G₁ – termed G₀.^[3] Subsequent research pointed to a restriction point (R-point) in G₁ where cells can enter G₀ before the R-point but are committed to mitosis after the R-point.^[4] These early studies provided evidence for the existence of a G₀ state to which access is restricted. These cells that do not divide further exit G₁ phase to enter an inactive stage called quiescent stage.