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Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast

Author

Listed:
  • Francesco Cambuli

    (Epigenetics Programme, The Babraham Institute
    Centre for Trophoblast Research, University of Cambridge)

  • Alexander Murray

    (Epigenetics Programme, The Babraham Institute
    Centre for Trophoblast Research, University of Cambridge)

  • Wendy Dean

    (Epigenetics Programme, The Babraham Institute)

  • Dominika Dudzinska

    (Epigenetics Programme, The Babraham Institute
    Centre for Trophoblast Research, University of Cambridge)

  • Felix Krueger

    (Bioinformatics Group, The Babraham Institute)

  • Simon Andrews

    (Bioinformatics Group, The Babraham Institute)

  • Claire E. Senner

    (Epigenetics Programme, The Babraham Institute
    Centre for Trophoblast Research, University of Cambridge)

  • Simon J. Cook

    (Signalling Programme, The Babraham Institute)

  • Myriam Hemberger

    (Epigenetics Programme, The Babraham Institute
    Centre for Trophoblast Research, University of Cambridge
    Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute)

Abstract

Embryonic (ES) and trophoblast (TS) stem cells reflect the first, irrevocable cell fate decision in development that is reinforced by distinct epigenetic lineage barriers. Nonetheless, ES cells can seemingly acquire TS-like characteristics upon manipulation of lineage-determining transcription factors or activation of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway. Here we have interrogated the progression of reprogramming in ES cell models with regulatable Oct4 and Cdx2 transgenes or conditional Erk1/2 activation. Although trans-differentiation into TS-like cells is initiated, lineage conversion remains incomplete in all models, underpinned by the failure to demethylate a small group of TS cell genes. Forced expression of these non-reprogrammed genes improves trans-differentiation efficiency, but still fails to confer a stable TS cell phenotype. Thus, even ES cells in ground-state pluripotency cannot fully overcome the boundaries that separate the first cell lineages but retain an epigenetic memory of their ES cell origin.

Suggested Citation

  • Francesco Cambuli & Alexander Murray & Wendy Dean & Dominika Dudzinska & Felix Krueger & Simon Andrews & Claire E. Senner & Simon J. Cook & Myriam Hemberger, 2014. "Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6538
    DOI: 10.1038/ncomms6538
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    Cited by:

    1. Moriyah Naama & Moran Rahamim & Valery Zayat & Shulamit Sebban & Ahmed Radwan & Dana Orzech & Rachel Lasry & Annael Ifrah & Mohammad Jaber & Ofra Sabag & Hazar Yassen & Areej Khatib & Silvina Epsztejn, 2023. "Pluripotency-independent induction of human trophoblast stem cells from fibroblasts," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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