RT Journal Article
SR Electronic
T1 Distinct SoxB1 networks are required for naïve and primed pluripotency
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 229716
DO 10.1101/229716
A1 Andrea Corsinotti
A1 Frederick C. K. Wong
A1 Tülin Tatar
A1 Iwona Szczerbinska
A1 Florian Halbritter
A1 Douglas Colby
A1 Sabine Gogolok
A1 Raphaël Pantier
A1 Kirsten Liggat
A1 Elham S. Mirfazeli
A1 Elisa Hall-Ponsele
A1 Nicholas Mullin
A1 Valerie Wilson
A1 Ian Chambers
YR 2017
UL http://biorxiv.org/content/early/2017/12/06/229716.abstract
AB Deletion of Sox2 from 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.