Distinct SoxB1 networks are required for naïve and primed pluripotency

Author:

Corsinotti Andrea12ORCID,Wong Frederick CK1,Tatar Tülin1,Szczerbinska Iwona1,Halbritter Florian1ORCID,Colby Douglas1,Gogolok Sabine1,Pantier Raphaël1,Liggat Kirsten1,Mirfazeli Elham S1,Hall-Ponsele Elisa1,Mullin Nicholas P1,Wilson Valerie1ORCID,Chambers Ian1ORCID

Affiliation:

1. MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland

2. Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan

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 naïve pluripotency.

Funder

Medical Research Council

Biotechnology and Biological Sciences Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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