Chen Xueran, Du Zhaoxia, Shi Wei, Wang Chen, Yang Yang, Wang Fen, Yao Yao, He Kun, Hao Aijun
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Infertility Center, Qilu Hospital, Shandong University School of Medicine, No. 44, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
Stem Cell Res. 2014 Mar;12(2):481-91. doi: 10.1016/j.scr.2013.12.010. Epub 2013 Dec 29.
In order to evaluate the functional significance of palmitoylation during multi-potent neural stem/progenitor cell proliferation and differentiation, retinoic acid-induced P19 cells were used in this study as a model system. Cell behaviour was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BP). Here, we observed a significant reduction in neuronal differentiation in the 2BP-treated cell model. We further explored the underlying mechanisms and found that 2BP resulted in the decreased acetylation of histones H3 and H4 and interfered with cell cycle withdrawal and neural stem/progenitor cells' renewal. Our results established a direct link between palmitoylation and the regulation of neural cell fate specification and revealed the epigenetic regulatory mechanisms that are involved in the effects of palmitoylation during neural development.
为了评估棕榈酰化在多能神经干细胞/祖细胞增殖和分化过程中的功能意义,本研究使用视黄酸诱导的P19细胞作为模型系统。在存在蛋白质棕榈酰化抑制剂2-溴棕榈酸酯(2BP)的情况下监测细胞行为。在此,我们观察到2BP处理的细胞模型中神经元分化显著降低。我们进一步探究了潜在机制,发现2BP导致组蛋白H3和H4的乙酰化减少,并干扰细胞周期退出和神经干细胞/祖细胞的更新。我们的结果建立了棕榈酰化与神经细胞命运决定调控之间的直接联系,并揭示了神经发育过程中棕榈酰化作用所涉及的表观遗传调控机制。