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Nat Commun. 2015 May 13;6:7095. doi: 10.1038/ncomms8095.

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

Author information

1
1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
2
1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France [3] Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
3
1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France [3] INRA, USC1361, 18 Avenue Doyen Lépine, Bron F-69500, France.
4
UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS, 300 Boulevard Sébastien Brant, BP 10413, Illkirch F-67412, France.
5
Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
6
UMR7216 Epigenetics and Cell Fate, CNRS, University of Paris Diderot, Sorbonne Paris Cité, Paris F-75013, France.
7
INRA, UMR1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet Tolosan F-31326, France.
8
1] INSERM, U1040, Montpellier F-34000, France [2] CHU Montpellier, Institute for Research in Biotherapy, Hôpital Saint-Eloi, Montpellier F-34000, France.
9
Department of Genetics, Lyon University Hospital, CNRS UMR 5292, INSERM U1028, Bron F-69500, France.

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.

PMID:
25968054
PMCID:
PMC4479042
DOI:
10.1038/ncomms8095
[Indexed for MEDLINE]
Free PMC Article

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