Critical Role for P53 in Regulating the Cell Cycle of Ground State Embryonic Stem Cells

Menno ter Huurne, Tianran Peng, Guoqiang Yi, Guido van Mierlo, Hendrik Marks, Hendrik G. Stunnenberg

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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 that is required for the elongated G1 phase characteristic of ground state ESCs. RNA sequencing and chromatin immunoprecipitation sequencing 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 reveal a mechanism by which inactivation of P53 can lead to loss of RB and uncontrolled cell proliferation.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalStem Cell Reports
Volume14
Issue number2
DOIs
Publication statusPublished - 11 Feb 2020
Externally publishedYes

Keywords

  • embryonic stem cells
  • G1 checkpoint
  • P53
  • RB

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