Data from: The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways

The neural fate commitment of pluripotent stem cells requires the repression of extrinsic inhibitory signals and the activation of intrinsic positive transcription factors. However, how these two events are integrated to ensure appropriate neural conversion remains unclear. Here, we showed that Pou3f1 is essential for the neural differentiation of mouse embryonic stem cells (ESCs), specifically during the transition from epiblast stem cells (EpiSCs) to neural progenitor cells (NPCs). Chimeric analysis showed that Pou3f1 knockdown leads to a markedly decreased incorporation of ESCs in the neuroectoderm. By contrast, Pou3f1-overexpressing ESC derivatives preferentially contribute to the neuroectoderm. Genome-wide ChIP-seq and RNA-seq analyses indicated that Pou3f1 is an upstream activator of neural lineage genes, and also is a repressor of BMP and Wnt signaling. Our results established that Pou3f1 promotes the neural fate commitment of pluripotent stem cells through a dual role, activating internal neural induction programs and antagonizing extrinsic neural inhibitory signals.

多能干细胞的神经命运决定，需要抑制外源抑制性信号并激活内源性正向转录因子。然而，这两类事件如何协同以保障恰当的神经转化过程，目前仍不明确。本研究发现，Pou3f1对小鼠胚胎干细胞（ESCs）的神经分化至关重要，其具体作用阶段为上胚层干细胞（EpiSCs）向神经前体细胞（NPCs）的转化过程。嵌合分析结果显示，Pou3f1基因敲低会显著降低ESCs在神经外胚层中的整合效率；与之相反，过表达Pou3f1的ESC衍生物则优先向神经外胚层分化。全基因组染色质免疫共沉淀测序（ChIP-seq）与RNA测序（RNA-seq）分析表明，Pou3f1既是神经谱系基因的上游激活因子，同时也是骨形态发生蛋白（BMP）与Wnt信号通路的抑制因子。本研究结果证实，Pou3f1通过双重功能促进多能干细胞的神经命运决定：一方面激活内源性神经诱导程序，另一方面拮抗外源神经抑制信号。