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Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency

Author

Listed:
  • Hongwei Chen

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Irène Aksoy

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon
    Stem Cell and Developmental Biology, Genome Institute of Singapore)

  • Fabrice Gonnot

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Pierre Osteil

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Maxime Aubry

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Claire Hamela

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Cloé Rognard

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Arnaud Hochard

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Sophie Voisin

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon
    INRA, USC1361)

  • Emeline Fontaine

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Magali Mure

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Marielle Afanassieff

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon
    INRA, USC1361)

  • Elouan Cleroux

    (UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS)

  • Sylvain Guibert

    (UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS)

  • Jiaxuan Chen

    (Stem Cell and Developmental Biology, Genome Institute of Singapore)

  • Céline Vallot

    (UMR7216 Epigenetics and Cell Fate, CNRS, University of Paris Diderot, Sorbonne Paris Cité)

  • Hervé Acloque

    (INRA, UMR1388 Génétique, Physiologie et Systèmes d’Elevage)

  • Clémence Genthon

    (INRA, UMR1388 Génétique, Physiologie et Systèmes d’Elevage)

  • Cécile Donnadieu

    (INRA, UMR1388 Génétique, Physiologie et Systèmes d’Elevage)

  • John De Vos

    (INSERM, U1040
    CHU Montpellier, Institute for Research in Biotherapy, Hôpital Saint-Eloi)

  • Damien Sanlaville

    (Lyon University Hospital, CNRS UMR 5292, INSERM U1028)

  • Jean- François Guérin

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Michael Weber

    (UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS)

  • Lawrence W Stanton

    (Stem Cell and Developmental Biology, Genome Institute of Singapore)

  • Claire Rougeulle

    (UMR7216 Epigenetics and Cell Fate, CNRS, University of Paris Diderot, Sorbonne Paris Cité)

  • Bertrand Pain

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon
    INRA, USC1361)

  • Pierre-Yves Bourillot

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

  • Pierre Savatier

    (INSERM, U846, Stem Cell and Brain Research Institute
    Université de Lyon)

Abstract

Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.

Suggested Citation

  • Hongwei Chen & Irène Aksoy & Fabrice Gonnot & Pierre Osteil & Maxime Aubry & Claire Hamela & Cloé Rognard & Arnaud Hochard & Sophie Voisin & Emeline Fontaine & Magali Mure & Marielle Afanassieff & Elo, 2015. "Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency," Nature Communications, Nature, vol. 6(1), pages 1-17, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8095
    DOI: 10.1038/ncomms8095
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    Cited by:

    1. Sébastien Durand & Marion Bruelle & Fleur Bourdelais & Bigitha Bennychen & Juliana Blin-Gonthier & Caroline Isaac & Aurélia Huyghe & Sylvie Martel & Antoine Seyve & Christophe Vanbelle & Annie Adrait , 2023. "RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Yan Bi & Zhifen Tu & Jianfeng Zhou & Xuehao Zhu & Hong Wang & Shaorong Gao & Yixuan Wang, 2022. "Cell fate roadmap of human primed-to-naive transition reveals preimplantation cell lineage signatures," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Francesco Panariello & Onelia Gagliano & Camilla Luni & Antonio Grimaldi & Silvia Angiolillo & Wei Qin & Anna Manfredi & Patrizia Annunziata & Shaked Slovin & Lorenzo Vaccaro & Sara Riccardo & Valenti, 2023. "Cellular population dynamics shape the route to human pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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