title: Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.
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.
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Irène
authors.initials: I
authors.lastname: Aksoy
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gonnot
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Osteil
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Aubry
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Hamela
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Cloé
authors.initials: C
authors.lastname: Rognard
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hochard
authors.affiliation: 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.
authors.forename: Sophie
authors.initials: S
authors.lastname: Voisin
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Emeline
authors.identifier: 0000000268858869
authors.initials: E
authors.lastname: Fontaine
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Mure
authors.affiliation: 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.
authors.forename: Marielle
authors.initials: M
authors.lastname: Afanassieff
authors.affiliation: UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS, 300 Boulevard Sébastien Brant, BP 10413, Illkirch F-67412, France.
authors.forename: Elouan
authors.initials: E
authors.lastname: Cleroux
authors.affiliation: UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS, 300 Boulevard Sébastien Brant, BP 10413, Illkirch F-67412, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Guibert
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Jiaxuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: UMR7216 Epigenetics and Cell Fate, CNRS, University of Paris Diderot, Sorbonne Paris Cité, Paris F-75013, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Vallot
authors.affiliation: INRA, UMR1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet Tolosan F-31326, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Acloque
authors.affiliation: INRA, UMR1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet Tolosan F-31326, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Genthon
authors.affiliation: INRA, UMR1388 Génétique, Physiologie et Systèmes d'Elevage, Castanet Tolosan F-31326, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Donnadieu
authors.affiliation: 1] INSERM, U1040, Montpellier F-34000, France [2] CHU Montpellier, Institute for Research in Biotherapy, Hôpital Saint-Eloi, Montpellier F-34000, France.
authors.forename: John
authors.identifier: 0000000318804130
authors.initials: J
authors.lastname: De Vos
authors.affiliation: Department of Genetics, Lyon University Hospital, CNRS UMR 5292, INSERM U1028, Bron F-69500, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Guérin
authors.affiliation: UMR 7242 Biotechnology and Cell Signaling, University of Strasbourg, CNRS, 300 Boulevard Sébastien Brant, BP 10413, Illkirch F-67412, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Weber
authors.affiliation: Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton
authors.affiliation: UMR7216 Epigenetics and Cell Fate, CNRS, University of Paris Diderot, Sorbonne Paris Cité, Paris F-75013, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Rougeulle
authors.affiliation: 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.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pain
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bourillot
authors.affiliation: 1] INSERM, U846, Stem Cell and Brain Research Institute, 18 Avenue Doyen Lépine, Bron F-69500, France [2] Université de Lyon, Lyon 138672, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Savatier
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D061252:Feeder Cells; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D039904:Pluripotent Stem Cells / Q000502:physiology*; D040081:Protein Array Analysis; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013629:Tamoxifen; D016222:Fibroblast Growth Factor 2