Distinct SoxB1 networks are required for naïve and primed pluripotency

Andrea Corsinotti; Frederick C K Wong; Tülin Tatar; Iwona Szczerbinska; Florian Halbritter; Douglas Colby; Sabine Gogolok; Raphaël Pantier; Kirsten Liggat; Elham S Mirfazeli; Elisa Hall-Ponsele; Nicholas P Mullin; Valerie Wilson; Ian Chambers

doi:10.7554/eLife.27746

Distinct SoxB1 networks are required for naïve and primed pluripotency

Andrea Corsinotti, Frederick C K Wong, Tülin Tatar, Iwona Szczerbinska, Florian Halbritter, Douglas Colby, Sabine Gogolok, Raphaël Pantier, Kirsten Liggat, Elham S Mirfazeli, Elisa Hall-Ponsele, Nicholas P Mullin, Valerie Wilson, Ian Chambers

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

Abstract / Description of output

Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.

Original language	English
Article number	e27746
Number of pages	28
Journal	eLIFE
Volume	6
DOIs	https://doi.org/10.7554/eLife.27746
Publication status	Published - 19 Dec 2017

Keywords / Materials (for Non-textual outputs)

embryonic stem cells
epiblast stem cells
pluripotency
sox
developmental biology
mouse
stem cells
transcription factors

Access to Document

10.7554/eLife.27746Licence: Creative Commons: Attribution (CC-BY)

ChambersEtaleLife2017DistinctSoxB1NetworksAreRequiredForBNaïveAndPrimedPluripotency
Copyright Corsinotti et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Final published version, 10.5 MBLicence: Creative Commons: Attribution (CC-BY)

Japan Partnering Award: Gene regulatory networks in stem cells and primordial germ cells
Chambers, I., Blackburn, C., Kunath, T., Lowell, S., Medvinsky, A., O'Carroll, D., Rosser, S., Soufi, A. & Wilson, V.
BBSRC
1/08/16 → 31/05/23
Project: Research
Dynamic transcription factor function in control of pluripotent cell sub-states
Chambers, I. & Tomlinson, S.
MRC
1/06/14 → 31/05/19
Project: Research
Pluripotency transcription factor function during primordial germ cell development
Chambers, I.
BBSRC
31/03/14 → 31/07/17
Project: Research

Role of Sox2 in preimplantation and postimplantation pluripotency
Corsinotti, A. (Creator), Wong, F. C. K. (Creator), Tatar, T. (Creator), Szczerbinska, I. (Creator), Halbritter, F. (Creator), Colby, D. (Creator), Gogolok, S. (Creator), Pantier, R. (Creator), Liggat, K. (Creator), Mirfazeli, E. S. (Creator), Hall-Ponsele, E. (Creator), Mullin, N. (Creator), Wilson, V. (Creator) & Chambers, I. (Creator), National Center for Biotechnology Information (Gene Expression Omnibus), 19 Dec 2017
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99185
Dataset

Ian Chambers
- School of Biological Sciences - Personal Chair in Pluripotent Stem Cell Biology
- Centre for Regenerative Medicine
Person: Academic: Research Active
Valerie Wilson
- v.wilsoned.acuk
- School of Biological Sciences - Personal Chair in Early Embryo Development
- Centre for Regenerative Medicine
Person: Academic: Research Active

Cite this

@article{a2d75dce8a55440fbe60059bc936a891,

title = "Distinct SoxB1 networks are required for na{\"i}ve and primed pluripotency",

abstract = "Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from na{\"i}ve pluripotency.",

keywords = "embryonic stem cells, epiblast stem cells, pluripotency, sox, developmental biology, mouse, stem cells, transcription factors",

author = "Andrea Corsinotti and Wong, {Frederick C K} and T{\"u}lin Tatar and Iwona Szczerbinska and Florian Halbritter and Douglas Colby and Sabine Gogolok and Rapha{\"e}l Pantier and Kirsten Liggat and Mirfazeli, {Elham S} and Elisa Hall-Ponsele and Mullin, {Nicholas P} and Valerie Wilson and Ian Chambers",

year = "2017",

month = dec,

day = "19",

doi = "10.7554/eLife.27746",

language = "English",

volume = "6",

journal = "eLIFE",

issn = "2050-084X",

publisher = "ELIFE SCIENCES PUBLICATIONS LTD",

}

TY - JOUR

T1 - Distinct SoxB1 networks are required for naïve and primed pluripotency

AU - Corsinotti, Andrea

AU - Wong, Frederick C K

AU - Tatar, Tülin

AU - Szczerbinska, Iwona

AU - Halbritter, Florian

AU - Colby, Douglas

AU - Gogolok, Sabine

AU - Pantier, Raphaël

AU - Liggat, Kirsten

AU - Mirfazeli, Elham S

AU - Hall-Ponsele, Elisa

AU - Mullin, Nicholas P

AU - Wilson, Valerie

AU - Chambers, Ian

PY - 2017/12/19

Y1 - 2017/12/19

N2 - Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.

AB - Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.

KW - embryonic stem cells

KW - epiblast stem cells

KW - pluripotency

KW - sox

KW - developmental biology

KW - mouse

KW - stem cells

KW - transcription factors

U2 - 10.7554/eLife.27746

DO - 10.7554/eLife.27746

M3 - Article

C2 - 29256862

SN - 2050-084X

VL - 6

JO - eLIFE

JF - eLIFE

M1 - e27746

ER -

Distinct SoxB1 networks are required for naïve and primed pluripotency

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

Japan Partnering Award: Gene regulatory networks in stem cells and primordial germ cells

Dynamic transcription factor function in control of pluripotent cell sub-states

Pluripotency transcription factor function during primordial germ cell development

Datasets

Role of Sox2 in preimplantation and postimplantation pluripotency

Profiles

Ian Chambers

Valerie Wilson

Cite this