- The mitotic cell cycle is traditionally divided into four phases: G₁ (Gap 1), S (DNA synthesis), G₂ (Gap 2), and M (mitosis). However, not all cells progress continuously through this cycle. In response to specific internal and external cues, proliferating cells may exit the cell cycle during the G₁ phase and enter a distinct state known as G₀.
- The G₀ phase is a non-proliferative state in which cells temporarily or permanently withdraw from the active cell cycle. It is often considered an “off-cycle” extension of G₁, because cells can enter G₀ from G₁ when conditions are not favourable for proliferation or when cell division is no longer required.
- Unlike damaged or dying cells, G₀ cells remain viable and metabolically active, carrying out their specialized functions. Most of our body cells are nonproliferative and are in the G0 phase.
- G₀ entry is regulated by both internal and external signals, including growth-factor availability, nutrient status, cell density, cell adhesion, differentiation signals, and environmental conditions.
- The G₀ phase may be reversible or permanent, depending on the cell type and the external signals involved. Reversible G₀ is also known as quiescence, a state in which cells can re‑enter the cell cycle when they receive the appropriate stimulus or conditions. In contrast, terminally differentiated cells remain permanently in G₀ and do not divide again.
- Far from representing a passive resting state, G₀ is a highly regulated cellular condition that plays essential roles in tissue maintenance, regeneration, differentiation, and protection against genomic instability.
- The concept of G₀ was first proposed to explain why many differentiated cells in multicellular organisms do not actively proliferate despite remaining viable. Today, G₀ is recognized as a diverse spectrum of cellular states ranging from reversible quiescence to irreversible cell-cycle withdrawal associated with terminal differentiation or senescence.
- Understanding the biology of G₀ has become increasingly important because dysregulation of quiescence contributes to ageing, cancer, tissue degeneration, and stem-cell dysfunction.
References/Further reading:
- Pardee A. B., 1974. A restriction point for control of normal animal cell proliferation. Proceedings of the National Academy of Sciences USA, 71, 1286–1290. PMID-4524638,
DOI: 10.1073/pnas.71.4.1286, PMCID: PMC388211 (Download PDF), PNAS (Download PDF)
Note: Classic paper establishing the concept of the restriction point and the relationship between G₁ progression and reversible quiescence. - Sun R & Buttitta L., 2017. States of G0 and the proliferation-quiescence decision in cells, tissues and during development. International Journal of Developmental Biology, 61, 357–366.
DOI: 10.1387/ijdb.160343LB, PMID-28695955,
Note: One of the most directly relevant reviews for an article specifically about G₀. It discusses G₀/quiescence, proliferation–quiescence decisions, tissue context, and developmental regulation. - Matson J.P., & Cook J.G., 2017. Cell cycle proliferation decisions: the impact of single cell analyses. FEBS Journal, 284, 362–375. DOI: 10.1111/febs.13898, PMID-27634578, PMCID: PMC5296213 (Download PDF), Wiley (Download PDF)
Note: Useful for understanding heterogeneity in cell-cycle entry and exit and why G₀ should not be viewed as a single uniform state. - Roche B., et al., 2017. Transcriptional reprogramming in cellular quiescence. RNA Biology, 14, 843–853. DOI: 10.1080/15476286.2017.1327510, PMID-28497998, PMCID: PMC5546717 (Download PDF), Tandfonline (Download PDF)
Note: Particularly relevant to your discussion of transcriptional repression/reprogramming during G₀.
