Cdk2 inhibition prolongs G1 phase progression in mouse embryonic stem cells
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19737069
DOI
10.1089/scd.2009.0065
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Cell Cycle drug effects MeSH
- HT29 Cells MeSH
- Time Factors MeSH
- Cyclin-Dependent Kinase 2 antagonists & inhibitors genetics metabolism MeSH
- Cyclin-Dependent Kinase 9 antagonists & inhibitors genetics metabolism MeSH
- Embryonic Stem Cells cytology drug effects metabolism MeSH
- G1 Phase drug effects MeSH
- Mice, Inbred Strains MeSH
- Inhibitory Concentration 50 MeSH
- Humans MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- CDC2 Protein Kinase antagonists & inhibitors genetics metabolism MeSH
- Flow Cytometry MeSH
- Purines pharmacology MeSH
- DNA Replication drug effects MeSH
- Cell Survival drug effects MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cdk2 protein, mouse MeSH Browser
- Cdk9 protein, mouse MeSH Browser
- Cyclin-Dependent Kinase 2 MeSH
- Cyclin-Dependent Kinase 9 MeSH
- olomoucine II MeSH Browser
- CDC2 Protein Kinase MeSH
- Purines MeSH
Embryonic stem cells (ESCs) proliferate rapidly and have a unique cell-cycle structure with a very short G1 phase. Previous reports suggested that the rapid G1 phase progression of ESCs might be underpinned by high and precocious Cdk2 activity and that Cdk2 activity might be crucial for both cell-cycle regulation and cell-fate decisions in human ESCs. However, the actual role of Cdk2 in cell-cycle progression of mouse ESCs (mESCs) has not been elucidated. In this study, we investigated the effects of down-regulation of Cdk2 activity by olomoucine II in 2 mESC lines. Olomoucine II treatment significantly increased the G1 phase cell numbers, decreased the S phase cell numbers, and inhibited DNA replication in mESCs. In nocodazole-synchronized mESCs, we show that specific down-regulation of Cdk2 activity prolongs G1 phase progression. In addition, down-regulation of Cdk2 activity in mESCs established a somatic cell-like cell cycle and induced expression of differentiation markers. Our results suggest that high Cdk2 activity is essential for rapid G1 phase progression and establishment of ESC-specific cell-cycle structure in mESCs and support the hypothesis of a link between cell-cycle regulation and pluripotency maintenance in ESCs. This study reveals olomoucine II to be an effective tool for manipulation of the cell cycle and pluripotency in ESCs and very likely also for the manipulation of other stem cell types, including cancer stem cells.
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