Editing G0 phase (section)

{{short description|Quiescent stage of the cell cycle in which the cell does not divide}}
{{DISPLAYTITLE:G<sub>0</sub> phase}}
[[File:Animal cell cycle-en.svg|right|thumb|350px|Mitosis in an [[animal cell]] (phases ordered counter-clockwise), with G<sub>0</sub> labeled at left.]]
[[Image:Gray626.png|thumb|right|200px|Many mammal [[cell (biology)|cells]], such as this 9x H [[neuron]], remain permanently or semipermanently in G<sub>0</sub>.]]

The '''G<sub>0</sub> phase''' describes a cellular state outside of the replicative [[cell cycle]]. Classically{{When|date=December 2023}}, cells were thought to enter G<sub>0</sub> primarily due to environmental factors, like nutrient deprivation, that limited the resources necessary for proliferation. Thus it was thought of as a '''''resting phase'''''. G<sub>0</sub> is now known to take different forms and occur for multiple reasons. For example, most adult [[neuron]]al cells, among the most metabolically active cells in the body, are fully differentiated and reside in a terminal G<sub>0</sub> phase. Neurons reside in this state, not because of stochastic or limited nutrient supply, but as a part of their developmental program.

G<sub>0</sub> 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 [[Cell growth|proliferate]] at similar rates.<ref name="HowardPelc2009">{{cite journal| vauthors = Howard A, Pelc SR |title=Synthesis of Desoxyribonucleic Acid in Normal and Irradiated Cells and Its Relation to Chromosome Breakage|journal=International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine|volume=49|issue=2|year=2009|pages=207–218|issn=0020-7616|doi=10.1080/09553008514552501}}</ref> 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.<ref name="Baserga2008">{{cite journal|last1=Baserga|first1=Renato | name-list-style = vanc |title=Biochemistry of the Cell Cycle: A Review |journal=Cell Proliferation|volume=1|issue=2|year=2008|pages=167–191|issn=0960-7722|doi=10.1111/j.1365-2184.1968.tb00957.x|s2cid=86353634 }}</ref> Early contrasting views either considered non-proliferating cells to simply be in an extended [[G1 phase|G<sub>1</sub> phase]] or in a cell cycle phase distinct from G<sub>1</sub> – termed G<sub>0</sub>.<ref name="Patt1963">{{cite journal | vauthors = Patt HM, Quastler H | title = Radiation effects on cell renewal and related systems | journal = Physiological Reviews | volume = 43 | issue = 3 | pages = 357–96 | date = July 1963 | pmid = 13941891 | doi = 10.1152/physrev.1963.43.3.357 }}</ref> Subsequent research pointed to a [[restriction point]] (R-point) in G<sub>1</sub> where cells can enter G<sub>0</sub> before the R-point but are committed to mitosis after the R-point.<ref name="Pardee1974">{{cite journal | vauthors = Pardee AB | title = A restriction point for control of normal animal cell proliferation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 71 | issue = 4 | pages = 1286–90 | date = April 1974 | pmid = 4524638 | pmc = 388211 | doi = 10.1073/pnas.71.4.1286 | bibcode = 1974PNAS...71.1286P | doi-access = free }}</ref> These early studies provided evidence for the existence of a G<sub>0</sub> state to which access is restricted. These cells that do not divide further exit G<sub>1</sub> phase to enter an inactive stage called '''quiescent stage.'''