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The RB family is required for the self-renewal and survival of human embryonic stem cells

Author

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  • Jamie F. Conklin

    (Stanford Medical School
    Stanford Medical School
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medical School)

  • Julie Baker

    (Stanford Medical School
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medical School)

  • Julien Sage

    (Stanford Medical School
    Stanford Medical School
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford Medical School)

Abstract

The mechanisms ensuring the long-term self-renewal of human embryonic stem cells are still only partly understood, limiting their use in cellular therapies. Here we found that increased activity of the RB cell cycle inhibitor in human embryonic stem cells induces cell cycle arrest, differentiation and cell death. Conversely, inactivation of the entire RB family (RB, p107 and p130) in human embryonic stem cells triggers G2/M arrest and cell death through functional activation of the p53 pathway and the cell cycle inhibitor p21. Differences in E2F target gene activation upon loss of RB family function between human embryonic stem cells, mouse embryonic stem cells and human fibroblasts underscore key differences in the cell cycle regulatory networks of human embryonic stem cells. Finally, loss of RB family function promotes genomic instability in both human and mouse embryonic stem cells, uncoupling cell cycle defects from chromosomal instability. These experiments indicate that a homeostatic level of RB activity is essential for the self-renewal and the survival of human embryonic stem cells.

Suggested Citation

  • Jamie F. Conklin & Julie Baker & Julien Sage, 2012. "The RB family is required for the self-renewal and survival of human embryonic stem cells," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2254
    DOI: 10.1038/ncomms2254
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    Cited by:

    1. Chao-Hui Chang & Feng Liu & Stefania Militi & Svenja Hester & Reshma Nibhani & Siwei Deng & James Dunford & Aniko Rendek & Zahir Soonawalla & Roman Fischer & Udo Oppermann & Siim Pauklin, 2024. "The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-29, December.

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