Distinct SoxB1 networks are required for naïve and primed pluripotency.
Distinct SoxB1 networks are required for naïve and primed pluripotency.
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DOI：
10.7554/elife.27746
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发表时间：
2017-12-19
期刊：
影响因子：
7.7
通讯作者：
Chambers I
中科院分区：
文献类型：
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作者：
Corsinotti A;Wong FC;Tatar T;Szczerbinska I;Halbritter F;Colby D;Gogolok S;Pantier R;Liggat K;Mirfazeli ES;Hall-Ponsele E;Mullin NP;Wilson V;Chambers I
从小鼠胚胎干细胞(ESCs)中缺失Sox2会导致滋养外胚层分化。虽然这可以通过强制表达相关的SOXB1蛋白SOX1或SOX3来阻止，但SOXB1蛋白在上皮细胞干细胞多能性中的作用尚不清楚。在这里，我们展示了Sox2可以从EpiSCs中删除而不受惩罚。这是由于EpiSCs中SoxB1的表达平衡发生了变化，与ESCs相比，EpiSCs中的Sox2减少，SOX3增加。与功能冗余一致，SOX3也可以从EpiSCs中删除，而不会消除自我更新。然而，同时删除SOX2和SOX3会阻止自我更新。胚胎干细胞中SOXB1的总体水平影响分化选择：Sox2杂合子ESCs的神经分化受到影响，而SOXB1水平的增加则将ESC向EpiSC的转变转向神经分化。因此，最佳的SOXB1水平对于每一种多能状态和退出天真多能性的细胞命运决定都是至关重要的。
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.