Lactate Activates Germline and Cleavage Embryo Genes in Mouse Embryonic Stem Cells

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 Zscan4 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.