GO:0045023 G0 to G1 transition: Quiescence Exit, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045023 (G0 to G1 transition) is the mitotic cell cycle phase transition that commits a quiescent G0 cell to re-enter G1 and resume growth and division.
• The transition is accompanied by extensive reprogramming of gene expression and can be visualized experimentally using the mVenus-p27K- indicator, which identifies quiescent cells and marks G0-G1 transition.
• D-type cyclins have CDK-independent roles in regulating DNA mismatch repair during this transition, expanding the known functions of G0-G1 regulators.
• Extracellular cues such as high-density lipoprotein (HDL) can promote G0-G1/S transition in fibroblasts, linking lipid metabolism to cell cycle re-entry.
• Cell contact between CD4 T cells and macrophages drives macrophage G0-G1 transition, demonstrating that immune interactions control quiescence exit.
• Dysregulation of G0-G1 transition is implicated in diseases including adenomyosis, where ARG2 knockdown promotes G0/G1 arrest via NF-kB and Wnt/beta-catenin signaling.
Description
The G0 to G1 transition (GO:0045023) is a critical cell cycle phase transition that determines whether a quiescent cell will re-enter the proliferative cycle. Quiescent cells reside in G0, a state of reversible growth arrest, and appropriate stimulation induces them to return to G1 and resume growth and division. This transition is accompanied by many changes in the program of gene expression, making it a focal point for understanding how cells integrate external signals to make fate decisions. Researchers study this process to uncover mechanisms of tissue regeneration, immune activation, and cancer dormancy. The ability to identify and track cells undergoing G0-G1 transition has been advanced by tools such as the mVenus-p27K- indicator, which specifically marks quiescent cells and visualizes the transition. Beyond classical cell cycle regulators, emerging evidence shows that proteins such as D-type cyclins have CDK-independent functions in DNA mismatch repair during this window, highlighting the complexity of this phase. Extracellular factors, including high-density lipoprotein, can also contribute to G0-G1/S transition in fibroblasts, linking metabolic signals to cell cycle re-entry. In the immune system, contact between CD4 T cells and macrophages drives macrophage G0-G1 transition, illustrating how intercellular communication controls quiescence exit. Dysregulation of this transition is associated with pathological states; for example, ARG2 knockdown promotes G0/G1 arrest and mitochondrial dysfunction in adenomyosis through NF-kB and Wnt/beta-catenin signaling. Thus, GO:0045023 represents a convergence point for cell cycle control, gene expression reprogramming, and disease mechanisms.
G0 to G1 transition At A Glance
| GO ID | GO:0045023 |
|---|---|
| GO term | G0 to G1 transition |
| Ontology | biological_process |
| Synonym | None |
| Major function | Commitment of quiescent G0 cells to re-enter G1 and resume growth and division |
| Definition source | QuickGO |
| Associated cellular state | Quiescence (G0) to proliferative cycle (G1) |
| Key experimental marker | mVenus-p27K- indicator for quiescent cells and G0-G1 transition |
| Example regulatory input | High-density lipoprotein promotes G0-G1/S transition in fibroblasts |
What Is GO:0045023?
GO:0045023 (G0 to G1 transition) is defined as the mitotic cell cycle phase transition whose occurrence commits the cell from the G0 quiescent state to the G1 phase. Under certain conditions, cells exit the cell cycle during G1 and remain in the G0 state as nongrowing, non-dividing (quiescent) cells. Appropriate stimulation of such cells induces them to return to G1 and resume growth and division. The G0 to G1 transition is accompanied by many changes in the program of gene expression.
Why Is G0 to G1 transition Important in Cell Biology?
The G0 to G1 transition is a decisive checkpoint in cell fate, determining whether a quiescent cell remains dormant or re-enters the proliferative cycle. This process is fundamental to tissue homeostasis, immune responses, and cancer biology, as it controls the reactivation of dormant cells and the initiation of proliferation. Understanding the molecular mechanisms of this transition can reveal therapeutic targets for diseases characterized by aberrant quiescence or proliferation, such as cancer and adenomyosis.
• Controls the exit from quiescence, a reversible state that cancer cells can exploit for dormancy and therapy resistance.
• Involved in immune activation, as CD4 T cell contact drives macrophage G0-G1 transition.
• Linked to metabolic regulation, with HDL promoting G0-G1/S transition in fibroblasts.
• Dysregulated in adenomyosis, where ARG2 knockdown causes G0/G1 arrest via NF-kB and Wnt/beta-catenin signaling.
• Requires extensive gene expression reprogramming, making it a model for studying transcriptional control of cell cycle entry.
• D-type cyclins have CDK-independent roles in DNA mismatch repair during this transition, connecting cell cycle re-entry to genome maintenance.
• Provides a target for experimental tools like the mVenus-p27K- indicator to identify and track quiescent cells.
• Relevant to lymphocyte biology, as deoxyadenosine can block G0 to G1 transition in lymphocytes via protein kinases.
• Involves nuclear architecture changes, such as repositioning of inactive X chromosomes during G0/G1 transition.
• Cyclin E is essential for the subsequent G1-to-S phase transition, highlighting the sequential nature of cell cycle re-entry.
What Happens During G0 to G1 transition?
Exit from Quiescence and Commitment to G1
In simple terms: A resting cell receives a signal to wake up and start preparing to divide.
The G0 to G1 transition begins when a quiescent cell receives appropriate stimulation, committing it to re-enter the cell cycle. This transition is accompanied by many changes in the program of gene expression, which drive the cell toward G1. The process can be visualized using the mVenus-p27K- indicator, which identifies quiescent cells and marks the G0-G1 transition.
Gene Expression Reprogramming
In simple terms: The cell switches on a new set of genes needed for growth and division.
The G0 to G1 transition is accompanied by many changes in the program of gene expression, enabling the cell to shift from a quiescent state to a growth-permissive state. This reprogramming is essential for the cell to resume growth and division.
Role of D-type Cyclins Beyond CDK Regulation
In simple terms: Proteins known for driving the cell cycle also have a separate job in fixing DNA errors.
D-type cyclins have a CDK-independent role in regulating DNA mismatch repair during the G0 to G1 transition, indicating that cell cycle regulators can have additional functions in genome maintenance.
Extracellular and Metabolic Inputs
In simple terms: Outside signals like lipids can push cells to re-enter the cycle.
High-density lipoprotein contributes to G0-G1/S transition in Swiss NIH/3T3 fibroblasts, demonstrating that extracellular metabolic factors can promote cell cycle re-entry. Additionally, CD4 T cell contact drives macrophage G0-G1 transition, showing that intercellular interactions regulate this process.
Nuclear Architecture Changes
In simple terms: The cell's nucleus reorganizes its chromosomes as it prepares to divide.
Changes in the position and volume of inactive X chromosomes occur during the G0/G1 transition, indicating that nuclear architecture is dynamically regulated during this phase.
Pharmacological and Signaling Modulation
In simple terms: Certain drugs or signaling pathways can block or promote this transition.
Deoxyadenosine can block the G0 to G1 transition in lymphocytes, possibly involving protein kinases. In adenomyosis, ARG2 knockdown promotes G0/G1 cell cycle arrest and mitochondrial dysfunction via regulation of NF-kB and Wnt/beta-catenin signaling cascades.
Key Genes Involved in GO:0045023 G0 to G1 transition
The following genes and proteins are experimentally implicated in the regulation or execution of the G0 to G1 transition (GO:0045023).
| Gene | Major Role | Research Relevance |
|---|---|---|
| CCND1 (Cyclin D1) | D-type cyclin; CDK-independent regulation of DNA mismatch repair during G0-G1 transition | Studied for CDK-independent functions in genome maintenance |
| CCNE1 (Cyclin E) | Essential for G1-to-S phase transition; nuclear protein | Key regulator of cell cycle progression after G0-G1 |
| CDKN1B (p27Kip1) | Cyclin-dependent kinase inhibitor; used in mVenus-p27K- indicator to mark quiescent cells | Tool for visualizing G0-G1 transition |
| ARG2 | Arginase 2; knockdown promotes G0/G1 arrest via NF-kB and Wnt/beta-catenin | Implicated in adenomyosis pathogenesis |
| NF-kB (e.g., RELA) | Signaling pathway regulating G0/G1 arrest upon ARG2 knockdown | Potential therapeutic target in adenomyosis |
| CTNNB1 (beta-catenin) | Wnt signaling component; involved in G0/G1 arrest regulation | Linked to ARG2 knockdown effects |
| CD4 (on T cells) | Mediates contact with macrophages driving G0-G1 transition | Immune cell cycle regulation |
| HDL-associated proteins | Contribute to G0-G1/S transition in fibroblasts | Metabolic control of cell cycle |
| Protein kinases (unspecified) | Involved in deoxyadenosine blockade of G0 to G1 transition in lymphocytes | Signaling mechanisms of quiescence exit |
| XIST (inactive X chromosome) | Position and volume changes during G0/G1 transition | Nuclear architecture dynamics |
| mVenus-p27K- (reporter) | Fusion protein indicator for quiescent cells and G0-G1 transition | Live-cell imaging of quiescence exit |
| D-type cyclins (CCND2, CCND3) | CDK-independent roles in DNA mismatch repair | Broader functions in cell cycle regulation |
| Cyclin E-CDK2 complex | Drives G1-to-S transition | Target for cell cycle inhibitors |
| ARG2-related mitochondrial proteins | Mitochondrial dysfunction upon ARG2 knockdown | Metabolic consequences of G0/G1 arrest |
| Wnt/beta-catenin pathway components | Regulate G0/G1 arrest in adenomyosis | Signaling cascade in disease |
| NF-kB pathway components | Regulate G0/G1 arrest in adenomyosis | Inflammatory signaling in cell cycle |
How Is G0 to G1 transition Regulated?
The G0 to G1 transition is regulated by a combination of extracellular signals, intracellular signaling cascades, and cell-cell interactions. High-density lipoprotein can promote G0-G1/S transition in fibroblasts, indicating metabolic regulation. CD4 T cell contact drives macrophage G0-G1 transition, showing immune-mediated control. Deoxyadenosine blocks this transition in lymphocytes, possibly through protein kinases. ARG2 knockdown promotes G0/G1 arrest via NF-kB and Wnt/beta-catenin signaling cascades in adenomyosis. Additionally, D-type cyclins regulate DNA mismatch repair independently of CDKs during this transition, adding a layer of regulation beyond canonical cell cycle control.
G0 to G1 transition and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ARG2 | Adenomyosis | ARG2 knockout or knockdown in endometrial cells; assess G0/G1 arrest and mitochondrial function |
| CCND1 | Cancer, DNA mismatch repair | CCND1 knockout or point mutant to separate CDK-dependent and independent functions |
| CCNE1 | Cancer, cell cycle progression | CCNE1 overexpression or knockout to study G1-to-S transition |
| CDKN1B (p27) | Quiescence regulation | mVenus-p27K- knock-in for live imaging of G0-G1 transition |
| NF-kB / beta-catenin | Adenomyosis, inflammation | Pathway reporters or knockouts in adenomyosis models |
Adenomyosis
ARG2 knockdown promotes G0/G1 cell cycle arrest and mitochondrial dysfunction in adenomyosis via regulation of NF-kB and Wnt/beta-catenin signaling cascades. This links the G0 to G1 transition to the pathogenesis of adenomyosis, suggesting that dysregulated quiescence exit contributes to disease.
Cancer and Cell Cycle Dysregulation
The G0 to G1 transition is critical for cancer dormancy and reactivation. D-type cyclins have CDK-independent roles in DNA mismatch repair during this transition, which may influence genome stability and tumor progression. Cyclin E is essential for the subsequent G1-to-S phase transition, and its dysregulation is associated with various cancers.
Immune Disorders
CD4 T cell contact drives macrophage G0-G1 transition, implicating this process in immune activation and inflammatory diseases. Deoxyadenosine blockade of G0 to G1 transition in lymphocytes suggests a role in lymphocyte biology and potential immunodeficiency or autoimmune conditions.
From G0 to G1 transition-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate gene regulate G0 to G1 transition? | CRISPR knockout in a quiescent cell model (e.g., fibroblasts) followed by stimulation and cell cycle analysis |
| What is the CDK-independent role of D-type cyclins in DNA mismatch repair? | Point mutation knock-in of CCND1 to disrupt CDK binding while preserving other functions |
| How does ARG2 knockdown affect G0/G1 arrest in adenomyosis? | ARG2 knockout or knockdown in endometrial cells; assess NF-kB and Wnt/beta-catenin signaling |
| Can we visualize G0-G1 transition in live cells? | Knock-in of mVenus-p27K- reporter |
| Does HDL promote G0-G1/S transition? | Overexpression or knockout of HDL receptors in NIH/3T3 fibroblasts |
| How does CD4 T cell contact drive macrophage G0-G1 transition? | Co-culture of CD4 T cells with macrophages; knockout of contact-dependent molecules |
How to Study the G0 to G1 transition Process
| Method | What It Measures | Typical Application |
|---|---|---|
| mVenus-p27K- imaging | Quiescent cells and G0-G1 transition | Live-cell tracking of cell cycle re-entry |
| Flow cytometry (DNA content) | Cell cycle phase distribution | Quantifying G0/G1 versus G1 populations |
| RNA-seq | Transcriptional changes | Identifying gene expression reprogramming during transition |
| Western blot | Protein expression and phosphorylation | Assessing signaling pathways (NF-kB, Wnt) |
| Immunofluorescence | Nuclear architecture and protein localization | Studying inactive X chromosome repositioning |
| Co-culture assays | Cell-cell contact effects | Macrophage G0-G1 transition driven by CD4 T cells |
| Kinase activity assays | Protein kinase function | Deoxyadenosine blockade of G0-G1 in lymphocytes |
| CRISPR screening | Gene function in transition | Identifying novel regulators of G0-G1 |
Live-Cell Imaging of G0-G1 Transition
The mVenus-p27K- indicator allows identification of quiescent cells and visualization of the G0-G1 transition in live cells. This method is useful for tracking cell cycle re-entry in real time.
Cell Cycle Analysis by Flow Cytometry
Flow cytometry using DNA dyes and markers such as Ki-67 or p27 can quantify the proportion of cells in G0/G1 versus G1 after stimulation. This is standard for assessing G0 to G1 transition.
Gene Expression Profiling
RNA-seq or microarray analysis can capture the extensive changes in the program of gene expression that accompany the G0 to G1 transition. This helps identify novel regulators and pathways.
Signaling Pathway Assays
Western blotting, luciferase reporters, and phospho-specific antibodies can measure activation of NF-kB, Wnt/beta-catenin, and protein kinases during G0 to G1 transition.
How CRISPR Can Be Used to Study GO:0045023 G0 to G1 transition
Knockout
CRISPR knockout of candidate genes such as ARG2 or CCND1 can reveal their requirement for G0 to G1 transition. For example, ARG2 knockdown promotes G0/G1 arrest in adenomyosis models, and CCND1 knockout can test CDK-independent functions in DNA mismatch repair.
Point Mutation
Point mutation knock-in can dissect specific domains or residues. For instance, mutating CDK-binding sites in D-type cyclins can separate their canonical cell cycle roles from CDK-independent functions in DNA mismatch repair during G0-G1 transition.
Knock-in
Knock-in of reporters such as mVenus-p27K- enables live visualization of G0-G1 transition. Tagged knock-in of endogenous genes can also track protein localization and dynamics during this transition.
Overexpression
Overexpression of genes like cyclin E or HDL-related factors can drive or enhance G0 to G1 transition, allowing gain-of-function studies. This is useful for identifying sufficiency of a factor to promote quiescence exit.
How EDITGENE Supports G0 to G1 transition Research
Researchers studying G0 to G1 transition-related genes often need to determine whether a candidate gene is causally involved in quiescence exit or simply correlated with it. CRISPR-based models provide the gold standard for establishing causality, from knockout to precise point mutations and reporter knock-ins.
Contact EDITGENE today to design your custom CRISPR model for G0 to G1 transition research.
Frequently Asked Questions About G0 to G1 transition
What is GO:0045023 G0 to G1 transition?
GO:0045023 is the mitotic cell cycle phase transition that commits a quiescent G0 cell to re-enter G1 and resume growth and division, accompanied by changes in gene expression.
What genes are involved in G0 to G1 transition?
Key genes include CCND1 (D-type cyclins), CCNE1 (cyclin E), CDKN1B (p27), ARG2, and signaling components of NF-kB and Wnt/beta-catenin pathways.
How is G0 to G1 transition measured?
It can be measured using the mVenus-p27K- indicator for live-cell imaging, flow cytometry for DNA content, and RNA-seq for gene expression changes.
What is the role of D-type cyclins in G0 to G1 transition?
D-type cyclins have a CDK-independent role in regulating DNA mismatch repair during the G0 to G1 transition, in addition to their canonical cell cycle functions.
Can HDL affect G0 to G1 transition?
Yes, high-density lipoprotein contributes to G0-G1/S transition in Swiss NIH/3T3 fibroblasts.
How do immune cells influence G0 to G1 transition?
CD4 T cell contact drives macrophage G0-G1 transition, demonstrating that intercellular interactions regulate quiescence exit.
What diseases are linked to G0 to G1 transition?
Dysregulation is implicated in adenomyosis, where ARG2 knockdown promotes G0/G1 arrest via NF-kB and Wnt/beta-catenin signaling, and in cancer through cyclin E and D-type cyclin functions.
What is the mVenus-p27K- reporter?
It is a novel cell-cycle indicator that identifies quiescent cells and visualizes the G0-G1 transition in live cells.
How does deoxyadenosine affect G0 to G1 transition?
Deoxyadenosine blocks the G0 to G1 transition in lymphocytes, possibly involving protein kinases.
What happens to inactive X chromosomes during G0/G1 transition?
Changes in the position and volume of inactive X chromosomes occur during the G0/G1 transition, reflecting nuclear architecture dynamics.
Conclusion
The G0 to G1 transition (GO:0045023) is a fundamental cell cycle decision point that integrates extracellular signals, metabolic cues, and intracellular reprogramming to determine whether a quiescent cell re-enters proliferation. Experimental tools such as the mVenus-p27K- indicator and CRISPR-based models have advanced our understanding of this process, revealing roles for D-type cyclins in DNA mismatch repair, HDL in promoting transition, and ARG2 in disease-associated arrest. Continued research into this transition will illuminate mechanisms of tissue homeostasis, immune activation, and cancer dormancy, offering new therapeutic opportunities.
References
- 1. Oki T et al.. 2014. A novel cell-cycle-indicator, mVenus-p27K-, identifies quiescent cells and visualizes G0-G1 transition.. Sci Rep 4:4012 PMID: 24500246
- 2. Rona G et al.. 2024. CDK-independent role of D-type cyclins in regulating DNA mismatch repair.. Mol Cell 84(7):1224-1242.e13 PMID: 38458201
- 3. Angius F et al.. 2015. High-density lipoprotein contribute to G0-G1/S transition in Swiss NIH/3T3 fibroblasts.. Sci Rep 5:17812 PMID: 26640042
- 4. Mlcochova P et al.. 2024. CD4 T cell contact drives macrophage cell cycle G0-G1 transition.. Signal Transduct Target Ther 9(1):348 PMID: 39668182
- 5. Xu Y et al.. 2024. ARG2 knockdown promotes G0/G1 cell cycle arrest and mitochondrial dysfunction in adenomyosis via regulation NF-κB and Wnt/Β-catenin signaling cascades.. Int Immunopharmacol 140:112817 PMID: 39116499
- 6. Sato T et al.. 1996. Deoxyadenosine blockade of G0 to G1 transition in lymphocytes: possible involvement of protein kinases.. J Cell Physiol 166(2):288-95 PMID: 8591988
- 7. Lyu G et al.. 2018. Changes in the position and volume of inactive X chromosomes during the G0/G1 transition.. Chromosome Res 26(3):179-189 PMID: 29679205
- 8. Ohtsubo M et al.. 1995. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition.. Mol Cell Biol 15(5):2612-24 PMID: 7739542
