G0 phase

The G₀ phase, or 'resting phase' is a period in the cell cycle in which cells exist in an inactive, non-cycling state. The mammalian cell division cycle is controlled with extreme precision to complete the duplication of the genome and the segregation of replicated chromosome to daughter cells. In the past, cells were thought to enter G₀ by default simply because of proliferation limits such as nutrient deprivation or contact inhibition. G₀ is now viewed as a way for cells to preserve important functions over a long period.

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. 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. 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. 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. These early studies provided evidence for the existence of a G₀ state to which access is restricted.

Three G₀ states exist and can be categorized as either reversible () or irreversible (senescent and differentiated). Each of these three states can be entered from the G₁ phase before the cell commits to the next round of the cell cycle. Quiescence refers to a reversible G₀ state where subpopulations of cells reside in a 'quiescent' state before entering the cell cycle after activation in response to extrinsic signals. Quiescent cells are often identified by low RNA content, lack of cell proliferation markers, and increased label retention indicating low cell turnover. Senescence is distinct from quiescence because senescence is an irreversible state that cells enter in response to DNA damage or degradation that would make a cell's progeny nonviable. Such DNA damage can occur from telomere shortening over many cell divisions as well as reactive oxygen species (ROS) exposure, oncogene activation, and cell-cell fusion. While senescent cells can no longer replicate, they remain able to perform many normal cellular functions. Senescence is often a biochemical alternative to the self-destruction of such a damaged cell by apoptosis. In contrast to cellular senescence, quiescence is not a reactive event but part of the core programming of several different cell types. Finally, differentiated cells are stem cells that have progressed through a differentiation program to reach a mature – terminally differentiated – state. Differentiated cells continue to stay in G₀ and perform their main functions indefinitely.

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