GSE202756
Lactate-dependent Transcriptional Regulation Controls Mammalian Eye Morphogenesis [H3Kla14 ChIP-seq]
Mammalian retinal metabolism utilizes aerobic glycolysis. However, the role of the glycolytic metabolism in retinal morphogenesis remains unknown. Here we report that aerobic glycolysis is critical during early stages of retinal development. Taking advantage of an unbiased approach that combined the use of eye organoids and single cell RNA sequencing we identified an enrichment in glycolytic genes in retina progenitors. Next, we determined that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we found that removal of GLUT1 and LDHA gene activity from developing retina progenitors impaired eye morphogenesis. Surprisingly, we uncovered that lactate- mediated histone lactylation is responsible for the upregulation of key eye field transcription factors. Our results identify lactate as a signaling molecule controlling mammalian eye morphogenesis. Overall design: Comparative histone h3 k14 lactylation (H3Kla14) profiling analysis of ChIP-seq data for the eye organoids and its treatments (control and GNE-140).