Document Detail


Cdk2 inhibition prolongs G1 phase progression in mouse embryonic stem cells.
MedLine Citation:
PMID:  19737069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Zuzana Koledova; Leona Raskova Kafkova; Lenka Calabkova; Vladimir Krystof; Petr Dolezel; Vladimir Divoky
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells and development     Volume:  19     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-26     Completed Date:  2010-06-03     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  181-94     Citation Subset:  IM    
Affiliation:
Department of Biology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
CDC2 Protein Kinase / antagonists & inhibitors,  genetics,  metabolism
Cell Cycle / drug effects
Cell Line
Cell Survival / drug effects
Cyclin-Dependent Kinase 2 / antagonists & inhibitors*,  genetics,  metabolism
Cyclin-Dependent Kinase 9 / antagonists & inhibitors,  genetics,  metabolism
DNA Replication / drug effects
Embryonic Stem Cells / cytology,  drug effects*,  metabolism
Flow Cytometry
G1 Phase / drug effects*
HT29 Cells
Humans
Inhibitory Concentration 50
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Purines / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Chemical
Reg. No./Substance:
0/Purines; 0/olomoucine II; EC 2.7.11.22/CDC2 Protein Kinase; EC 2.7.11.22/Cdk2 protein, mouse; EC 2.7.11.22/Cdk9 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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