Abstract:
In spite of its essential role in culture media, the precise influence of lactate on early mouse embryonic development remains elusive. Previous studies have implicated lactate accumulation in medium affecting histone acetylation. Recent research has underscored lactate-derived histone lactylation as a novel epigenetic modification in diverse cellular processes and diseases. Our investigation demonstrated that the absence of sodium lactate in the medium resulted in a pronounced 2-cell arrest at the late G2 phase in embryos. RNA-seq analysis revealed that the absence of sodium lactate significantly impaired the maternal-to-zygotic transition (MZT), particularly in zygotic gene activation (ZGA). Investigations were conducted employing Cut&Tag assays targeting the well-studied histone acetylation and lactylation sites, H3K18la and H3K27ac, respectively. The findings revealed a noticeable reduction in H3K18la modification under lactate deficiency, and this alteration showed a significant correlation with changes in gene expression. In contrast, H3K27ac exhibited minimal correlation. These results suggest that lactate may preferentially influence early embryonic development through H3K18la rather than H3K27ac modifications.
摘要:
尽管它在文化传媒中的重要作用,乳酸对小鼠早期胚胎发育的精确影响仍然难以捉摸。先前的研究涉及培养基中乳酸的积累影响组蛋白乙酰化。最近的研究强调了乳酸来源的组蛋白的乳酸化作为一种新的表观遗传修饰在不同的细胞过程和疾病。我们的研究表明,培养基中不存在乳酸钠会导致胚胎在G2晚期明显的2细胞停滞。RNA-seq分析显示,乳酸钠的缺乏显着损害了母体到合子的转换(MZT),特别是在合子基因激活(ZGA)中。采用Cut&Tag分析进行了研究,目标是研究良好的组蛋白乙酰化和乳酸化位点,H3K18la和H3K27ac,分别。研究结果表明,在乳酸缺乏的情况下,H3K18la修饰明显减少,这种改变与基因表达的变化显着相关。相比之下,H3K27ac表现出最小的相关性。这些结果表明,乳酸可能优先通过H3K18la而不是H3K27ac修饰影响早期胚胎发育。