Distinct SoxB1 networks are required for naïve and primed pluripotency

Deletion of 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 can be del...

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Published in:eLife 2017-12, Vol.6
Main Authors: Corsinotti, Andrea, Wong, Frederick Ck, Tatar, Tülin, Szczerbinska, Iwona, Halbritter, Florian, Colby, Douglas, Gogolok, Sabine, Pantier, Raphaël, Liggat, Kirsten, Mirfazeli, Elham S, Hall-Ponsele, Elisa, Mullin, Nicholas P, Wilson, Valerie, Chambers, Ian
Format: Article
Language:English
Subjects:
Animals
Cell fate
Cell self-renewal
Clonal deletion
Deoxyribonucleic acid
DNA
Embryo cells
Embryonic stem cells
Epiblast stem cells
Gene expression
Gene Expression Regulation
Gene Regulatory Networks
Germ Layers - embryology
Immunoglobulins
Mice
Microscopy
Mouse Embryonic Stem Cells - physiology
Pluripotency
Principal components analysis
Proteins
Sox
SOXB1 Transcription Factors - metabolism
Stem cell transplantation
Stem cells
Stem Cells and Regenerative Medicine
transcription factors
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Summary:Deletion of 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 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, can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both and prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.27746