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

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 Coninck, B. Menten, P. Mestdagh, J. Van de Sompele, D. Deforce, P. De Sutter and B. Heindryckx ()
Additional contact information
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
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
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

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15055

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