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

Hongwei Chen; Irène Aksoy; Fabrice Gonnot; Pierre Osteil; Maxime Aubry; Claire Hamela; Cloé Rognard; Arnaud Hochard; Sophie Voisin; Emeline Fontaine; Magali Mure; Marielle Afanassieff; Elouan Cleroux; Sylvain Guibert; Jiaxuan Chen; Céline Vallot; Hervé Acloque; Clémence Genthon; Cécile Donnadieu; John De Vos; Damien Sanlaville; Jean François Guérin; Michael Weber; Lawrence W. Stanton; Claire Rougeulle; Bertrand Pain; Pierre Yves Bourillot; Pierre Savatier

doi:10.1038/ncomms8095

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

Hongwei Chen, Irène Aksoy, Fabrice Gonnot, Pierre Osteil, Maxime Aubry, Claire Hamela, Cloé Rognard, Arnaud Hochard, Sophie Voisin, Emeline Fontaine, Magali Mure, Marielle Afanassieff, Elouan Cleroux, Sylvain Guibert, Jiaxuan Chen, Céline Vallot, Hervé Acloque, Clémence Genthon, Cécile Donnadieu, John De VosDamien Sanlaville, Jean François Guérin, Michael Weber, Lawrence W. Stanton, Claire Rougeulle, Bertrand Pain, Pierre Yves Bourillot, Pierre Savatier^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

144 Citations (Scopus)

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.

Original language	English
Article number	7095
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8095
Publication status	Published - 13 May 2015
Externally published	Yes

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Chen, H., Aksoy, I., Gonnot, F., Osteil, P., Aubry, M., Hamela, C., Rognard, C., Hochard, A., Voisin, S., Fontaine, E., Mure, M., Afanassieff, M., Cleroux, E., Guibert, S., Chen, J., Vallot, C., Acloque, H., Genthon, C., Donnadieu, C., ... Savatier, P. (2015). Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency. Nature Communications, 6, Article 7095. https://doi.org/10.1038/ncomms8095

@article{b4733b787ac74e43a68af3bb0c01e44c,

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.",

author = "Hongwei Chen and Ir{\`e}ne Aksoy and Fabrice Gonnot and Pierre Osteil and Maxime Aubry and Claire Hamela and Clo{\'e} Rognard and Arnaud Hochard and Sophie Voisin and Emeline Fontaine and Magali Mure and Marielle Afanassieff and Elouan Cleroux and Sylvain Guibert and Jiaxuan Chen and C{\'e}line Vallot and Herv{\'e} Acloque and Cl{\'e}mence Genthon and C{\'e}cile Donnadieu and {De Vos}, John and Damien Sanlaville and Gu{\'e}rin, {Jean Fran{\c c}ois} and Michael Weber and Stanton, {Lawrence W.} and Claire Rougeulle and Bertrand Pain and Bourillot, {Pierre Yves} and Pierre Savatier",

year = "2015",

month = may,

day = "13",

doi = "10.1038/ncomms8095",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

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Chen, H, Aksoy, I, Gonnot, F, Osteil, P, Aubry, M, Hamela, C, Rognard, C, Hochard, A, Voisin, S, Fontaine, E, Mure, M, Afanassieff, M, Cleroux, E, Guibert, S, Chen, J, Vallot, C, Acloque, H, Genthon, C, Donnadieu, C, De Vos, J, Sanlaville, D, Guérin, JF, Weber, M, Stanton, LW, Rougeulle, C, Pain, B, Bourillot, PY & Savatier, P 2015, 'Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency', Nature Communications, vol. 6, 7095. https://doi.org/10.1038/ncomms8095

TY - JOUR

T1 - Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency

AU - Chen, Hongwei

AU - Aksoy, Irène

AU - Gonnot, Fabrice

AU - Osteil, Pierre

AU - Aubry, Maxime

AU - Hamela, Claire

AU - Rognard, Cloé

AU - Hochard, Arnaud

AU - Voisin, Sophie

AU - Fontaine, Emeline

AU - Mure, Magali

AU - Afanassieff, Marielle

AU - Cleroux, Elouan

AU - Guibert, Sylvain

AU - Chen, Jiaxuan

AU - Vallot, Céline

AU - Acloque, Hervé

AU - Genthon, Clémence

AU - Donnadieu, Cécile

AU - De Vos, John

AU - Sanlaville, Damien

AU - Guérin, Jean François

AU - Weber, Michael

AU - Stanton, Lawrence W.

AU - Rougeulle, Claire

AU - Pain, Bertrand

AU - Bourillot, Pierre Yves

AU - Savatier, Pierre

PY - 2015/5/13

Y1 - 2015/5/13

N2 - 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.

AB - 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.

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U2 - 10.1038/ncomms8095

DO - 10.1038/ncomms8095

M3 - Article

C2 - 25968054

AN - SCOPUS:84929359290

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7095

ER -

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

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