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bioRxiv · 10.1101/674960

Critical role for P53 in regulating the cell cycle of ground state embryonic stem cells

ter Huurne, M.·Peng, T.·Yi, G.·van Mierlo, G.·Marks, H.·Stunnenberg, H.
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Abstract

Mouse Embryonic Stem Cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1-phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and modulates G1-phase progression. Our data shows that the elongated G1-phase characteristic of ground state ESCs is dependent on P53. RNA-seq and ChIP-seq analyses reveal that P53 directly regulates the expression of the Retinoblastoma (RB) protein and that the hypo-phosphorylated, active RB protein plays a key role in G1-phase control. Our findings suggest that the P53-P21 pathway is active in ground state 2i ESCs and that its role in the G1-checkpoint is abolished in serum ESCs. Taken together, the data reveals a mechanism by which inactivation of P53 can lead to loss of RB and uncontrolled cell proliferation.

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ter Huurne, M., Peng, T., Yi, G., van Mierlo, G., Marks, H., Stunnenberg, H.. 2019-06-18. Critical role for P53 in regulating the cell cycle of ground state embryonic stem cells. https://doi.org/10.1101/674960

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