Cell fate determination during G1 phase progression

Blomen, Vincent A.; Boonstra, Johannes

doi:10.1007/s00018-007-7271-z

Cited by 96 publications

(109 citation statements)

References 140 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…This protein associates with CDK4 or CDK6 and phosphorylates retinoblastoma protein, Rb. Rb functions as a tumor suppressor, and it is active in its hypophosphorylated form and repressed cell cycle progression by inhibiting E2F transcription factors which are necessary for S phase entry (Blomen and Boonstra 2007). To elucidate the mechanism of cell cycle arrest, the expression of cell cycle checkpoints proteins, CDK4 and CDK6, were determined.…”

Section: Resultsmentioning

confidence: 99%

Anti-proliferative effect of pterostilbene on rat hepatoma cells in culture

2014

View full text Add to dashboard Cite

Pterostilbene, a methoxylated analogue of resveratrol, is a natural compound primarily found in blueberries and several types of grapes. However, little is known about the effect of pterostilbene on the proliferation of hepatoma cells and its modes of actions. This study was undertaken to characterize its ability to suppress the proliferation of hepatoma AH109A cells and the possible mechanism(s) involved. Pterostilbene showed a significant and dose-dependent effect on the anti-proliferative activity against AH109A cells. Pterostilbene exerted little or no effect on the proliferation of rat L6 myoblasts and rat skin fibroblasts. Pterostilbeneloaded rat sera could significantly inhibit the proliferation of AH109A cells, which suggests that pterostilbene could be absorbed through gastrointestinal tract and retain its anti-proliferative activity. Pterostilbene arrested the cell cycle of AH109A cells at G0/ G1 phase and reduced the protein expression of cyclindependent kinase 4 and cyclin-dependent kinase 6 dose-dependently. We also found that pterostilbene could significantly increase the intracellular peroxide level of AH109A cells, which may be involved in its anti-proliferative activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Anti-proliferative effect of pterostilbene on rat hepatoma cells in culture

2014

View full text Add to dashboard Cite

show abstract

“…The fate decision is often made in the G1 phase of the cell cycle in which the cell may utilize an early checkpoint that can determine the cell's fate choice upon detection of DNA damage or stress stimuli (Blomen and Boonstra, 2007).…”

Section: Discussionmentioning

confidence: 99%

Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells

et al. 2008

View full text Add to dashboard Cite

One of the characteristic features of human embryonic stem cells (hESCs) is the competence for self-renewal and pluripotency. To date, little is known about cell cycle regulation in these cells and how the cell cycle machinery influences hESCs properties. A common feature of human, murine and primate ESCs is the presence of a short G1 phase, which has been viewed as a time window during which stem cells are exposed to differentiation signals. We used the hESCs differentiation model and comparisons to human embryonic carcinoma (EC) cells to study the key regulators of G1 to S transition in hESCs. Our studies show that hESCs express all G1-specific CYCLINs (D1, D2, D3 and E) and cyclin-dependent kinases (CDK) (CDK2, CDK4 and CDK6) at variable levels. In contrast to murine ESCs, most of the cell cycle regulators in hESCs show cell cycle-dependent expression, thus revealing important differences in the expression of cell cycle regulatory components between these two embryonic cell types. Knockdown of CDK2 using RNA interference resulted in hESCs arrest at G1 phase of the cell cycle and differentiation to extraembryonic lineages. This suggests an important role for CDK2 in cell cycle regulation in hESCs that are likely to bear significant impacts on the maintenance of their pluripotent phenotype.

show abstract

“…It has long been recognized that the G1 phase is a flexible period during which cells integrate multiple inputs from the environment [1][2][3]. Signal consolidation at the G1 phase may determine whether the cells will proliferate, differentiate, undergo apoptosis, or regress into quiescent state known as G0.…”

Section: Introductionmentioning

confidence: 99%

Human Embryonic Stem Cells Exhibit Increased Propensity to Differentiate During the G1 Phase Prior to Phosphorylation of Retinoblastoma Protein

et al. 2012

View full text Add to dashboard Cite

While experimentally induced arrest of human embryonic stem cells (hESCs) in G1 has been shown to stimulate differentiation, it remains unclear whether the unperturbed G1 phase in hESCs is causally related to differentiation. Here, we use centrifugal elutriation to isolate and investigate differentiation propensities of hESCs in different phases of their cell cycle. We found that isolated G1 cells exhibit higher differentiation propensity compared with S and G2 cells, and they differentiate at low cell densities even under self-renewing conditions. This differentiation of G1 cells was partially prevented in dense cultures of these cells and completely abrogated in coculture with S and G2 cells. However, coculturing without cell-to-cell contact did not rescue the differentiation of G1 cells. Finally, we show that the subset of G1 hESCs with reduced phosphorylation of retinoblastoma has the highest propensity to differentiate and that the differentiation is preceded by cell cycle arrest. These results provide direct evidence for increased propensity of hESCs to differentiate in G1 and suggest a role for neighboring cells in preventing differentiation of hESCs as they pass through a differentiation sensitive, G1 phase.

show abstract

Cell fate determination during G1 phase progression

Cited by 96 publications

References 140 publications

Anti-proliferative effect of pterostilbene on rat hepatoma cells in culture

Anti-proliferative effect of pterostilbene on rat hepatoma cells in culture

Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells

Human Embryonic Stem Cells Exhibit Increased Propensity to Differentiate During the G1 Phase Prior to Phosphorylation of Retinoblastoma Protein

Contact Info

Product

Resources

About