Cancer Institute A national cancer institute
designated cancer center

Julien Sage

Publication Details

  • The RB family is required for the self-renewal and survival of human embryonic stem cells NATURE COMMUNICATIONS Conklin, J. F., Baker, J., Sage, J. 2012; 3

    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.

    View details for DOI 10.1038/ncomms2254

    View details for Web of Science ID 000316356700012

    View details for PubMedID 23212373

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