Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cells. 2022 Feb 4;11(3):548. doi: 10.3390/cells11030548.
Lactate was recently found to mediate histone lysine lactylation and facilitate polarization of M1 macrophages, indicating its role in metabolic regulation of gene expression. During somatic cell reprogramming, lactate promotes histone lactylation of pluripotency genes and improves reprogramming efficiency. However, the function of lactate in cell fate control in embryonic stem cells (ESCs) remains elusive. In this study, we revealed that lactate supplementation activated germline genes in mouse ESCs. Lactate also induced global upregulation of cleavage embryo genes, such as members of the gene family. Further exploration demonstrated that lactate stimulated H3K18 lactylation accumulation on germline and cleavage embryo genes, which in turn promoted transcriptional elongation. Our findings indicated that lactate supplementation expanded the transcriptional network in mouse ESCs.
最近发现,乳酸可介导组蛋白赖氨酸乳酸化,促进 M1 巨噬细胞极化,提示其在基因表达的代谢调控中发挥作用。在体细胞重编程过程中,乳酸促进多能性基因的组蛋白乳酸化,提高重编程效率。然而,乳酸在胚胎干细胞(ESCs)中对细胞命运控制的功能仍不清楚。在这项研究中,我们揭示了补充乳酸可激活小鼠 ESCs 中的种系基因。乳酸还诱导了胚胎基因的全面上调,如基因家族的成员。进一步的探索表明,乳酸刺激种系和胚胎基因上 H3K18 乳酸化的积累,从而促进转录延伸。我们的研究结果表明,补充乳酸可扩展小鼠 ESCs 中的转录网络。