Yang Xuan, Zhou Wenjuan, Zhou Juan, Li Anna, Zhang Changqing, Fang Zhenya, Wang Chunying, Liu Shiyu, Hao Aijun, Zhang Meihua
Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, China.
Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Key Laboratory of Mental Disorders, Department of Anatomy and Histoembryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Heliyon. 2024 Mar 6;10(6):e27634. doi: 10.1016/j.heliyon.2024.e27634. eCollection 2024 Mar 30.
Polycomb group RING finger (PCGF) proteins, a crucial subunits of the Polycomb complex, plays an important role in regulating gene expression, embryonic development, and cell fate determination. In our research, we investigated Pcgf5, one of the six PCGF homologs, and its impact on the differentiation of P19 cells into neural stem cells. Our findings revealed that knockdown of Pcgf5 resulted in a significant decrease in the expression levels of the neuronal markers Sox2, Zfp521, and Pax6, while the expression levels of the pluripotent markers Oct4 and Nanog increased. Conversely, Pcgf5 overexpression upregulated the expression of Sox2 and Pax6, while downregulating the expression of Oct4 and Nanog. Additionally, our analysis revealed that Pcgf5 suppresses Wnt3 expression via the activation of Notch1/Hes1, and ultimately governs the differentiation fate of neural stem cells. To further validate our findings, we conducted experiments in zebrafish. We found that knockdown of pcgf5a using morpholino resulted in the downregulated expression of neurodevelopmental genes such as sox2, sox3, and foxg1 in zebrafish embryos. Consequently, these changes led to neurodevelopmental defects. In conclusion, our study highlights the important role of Pcgf5 in neural induction and the determination of neural cell fate.
多梳蛋白环指（PCGF）蛋白是多梳复合体的关键亚基，在调节基因表达、胚胎发育和细胞命运决定中发挥重要作用。在我们的研究中，我们研究了六个PCGF同源物之一的Pcgf5及其对P19细胞分化为神经干细胞的影响。我们的研究结果表明，敲低Pcgf5会导致神经元标记物Sox2、Zfp521和Pax6的表达水平显著降低，而多能性标记物Oct4和Nanog的表达水平则升高。相反，Pcgf5过表达会上调Sox2和Pax6的表达，同时下调Oct4和Nanog的表达。此外，我们的分析表明，Pcgf5通过激活Notch1/Hes1抑制Wnt3表达，并最终控制神经干细胞的分化命运。为了进一步验证我们的发现，我们在斑马鱼中进行了实验。我们发现，使用吗啉代敲低pcgf5a会导致斑马鱼胚胎中神经发育基因如sox2、sox3和foxg1的表达下调。因此，这些变化导致了神经发育缺陷。总之，我们的研究突出了Pcgf5在神经诱导和神经细胞命运决定中的重要作用。
