Editing G0 phase (section)

== <span id="&nbsp;Regulation of Quiescence"></span>Regulation of quiescence ==

=== <span id="&nbsp;Cell Cycle Regulators"></span>Cell cycle regulators ===
Functional [[tumor suppressor genes]], particularly [[p53]] and [[Rb gene]], are required to maintain stem cell quiescence and prevent exhaustion of the [[progenitor cell]] pool through excessive divisions. For example, deletion of all three components of the Rb family of proteins has been shown to halt quiescence in hematopoietic stem cells. Lack of p53 has been shown to prevent differentiation of these stem cells due to the cells' inability to exit the cell cycle into the G<sub>0</sub> phase. In addition to p53 and Rb, [[cyclin dependent kinase]] inhibitors (CKIs), such as [[p21]], [[CDKN1B|p27]], and [[p57 (gene)|p57]], are also important for maintaining quiescence. In mouse hematopoietic stem cells, knockout of p57 and p27 leads to G<sub>0</sub> exit through nuclear import of [[cyclin D1]] and subsequent [[phosphorylation]] of Rb. Finally, the [[Notch signaling pathway]] has been shown to play an important role in maintenance of quiescence.<ref name="CheungRando2013"/>

===Post-transcriptional regulation===
Post-transcriptional regulation of gene expression via [[miRNA]] synthesis has been shown to play an equally important role in the maintenance of stem cell quiescence. miRNA strands bind to the 3′ untranslated region ([[3′ UTR]]) of target [[mRNA]]s, preventing their translation into functional proteins. The length of the 3′ UTR of a gene determines its ability to bind to miRNA strands, thereby allowing regulation of quiescence. Some examples of miRNA's in stem cells include miR-126, which controls the [[PI3K/AKT/mTOR pathway]] in hematopoietic stem cells, miR-489, which suppresses the DEK [[oncogene]] in muscle stem cells, and miR-31, which regulates [[Myf5]] in muscle stem cells. miRNA sequestration of mRNA within [[ribonucleoprotein]] complexes allows quiescent cells to store the mRNA necessary for quick entry into the [[G1 phase]].<ref name="CheungRando2013"/>

=== <span id="&nbsp;Response to Stress"></span>Response to stress ===
Stem cells that have been quiescent for a long time often face various environmental stressors, such as [[oxidative stress]]. However, several mechanisms allow these cells to respond to such stressors. For example, the [[FOXO]] transcription factors respond to the presence of [[reactive oxygen species]] (ROS) while [[HIF1A]] and [[LKB1]] respond to [[Hypoxia (medical)|hypoxic]] conditions. In hematopoietic stem cells, [[autophagy]] is induced to respond to metabolic stress.<ref name="CheungRando2013"/>