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Direct comparison of distinct naive pluripotent states in human embryonic stem cells

Author

Listed:
  • S. Warrier

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • M. Van der Jeught

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • G. Duggal

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital
    John Radcliffe Hospital, University of Oxford)

  • L. Tilleman

    (Laboratory for Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University)

  • E. Sutherland

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • J. Taelman

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • M. Popovic

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • S. Lierman

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • S. Chuva De Sousa Lopes

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital
    Leiden University Medical Center)

  • A. Van Soom

    (Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University)

  • L. Peelman

    (Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University)

  • F. Van Nieuwerburgh

    (Laboratory for Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University)

  • D. I. M. De Coninck

    (Laboratory for Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University)

  • B. Menten

    (Center for Medical Genetics, Ghent University Hospital)

  • P. Mestdagh

    (Center for Medical Genetics, Ghent University Hospital)

  • J. Van de Sompele

    (Center for Medical Genetics, Ghent University Hospital)

  • D. Deforce

    (Laboratory for Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University)

  • P. De Sutter

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

  • B. Heindryckx

    (Ghent-Fertility and Stem cell Team (G-FaST), Ghent University Hospital)

Abstract

Until recently, human embryonic stem cells (hESCs) were shown to exist in a state of primed pluripotency, while mouse embryonic stem cells (mESCs) display a naive or primed pluripotent state. Here we show the rapid conversion of in-house-derived primed hESCs on mouse embryonic feeder layer (MEF) to a naive state within 5–6 days in naive conversion media (NCM-MEF), 6–10 days in naive human stem cell media (NHSM-MEF) and 14–20 days using the reverse-toggle protocol (RT-MEF). We further observe enhanced unbiased lineage-specific differentiation potential of naive hESCs converted in NCM-MEF, however, all naive hESCs fail to differentiate towards functional cell types. RNA-seq analysis reveals a divergent role of PI3K/AKT/mTORC signalling, specifically of the mTORC2 subunit, in the different naive hESCs. Overall, we demonstrate a direct evaluation of several naive culture conditions performed in the same laboratory, thereby contributing to an unbiased, more in-depth understanding of different naive hESCs.

Suggested Citation

  • S. Warrier & M. Van der Jeught & G. Duggal & L. Tilleman & E. Sutherland & J. Taelman & M. Popovic & S. Lierman & S. Chuva De Sousa Lopes & A. Van Soom & L. Peelman & F. Van Nieuwerburgh & D. I. M. De, 2017. "Direct comparison of distinct naive pluripotent states in human embryonic stem cells," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15055
    DOI: 10.1038/ncomms15055
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