RRC ID 76617
著者 Takata N, Miska JM, Morgan MA, Patel P, Billingham LK, Joshi N, Schipma MJ, Dumar ZJ, Joshi NR, Misharin AV, Embry RB, Fiore L, Gao P, Diebold LP, McElroy GS, Shilatifard A, Chandel NS, Oliver G.
タイトル Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis.
ジャーナル Nat Commun
Abstract Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development. Taking advantage of an unbiased approach that combines the use of eye organoids and single-cell RNA sequencing, we identify specific glucose transporters and glycolytic genes in retinal progenitors. Next, we determine that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we show that removal of Glucose transporter 1 and Lactate dehydrogenase A gene activity from developing retinal progenitors arrests eye morphogenesis. Surprisingly, we uncover that lactate-mediated upregulation of key eye-field transcription factors is controlled by the epigenetic modification of histone H3 acetylation through histone deacetylase activity. Our results identify an unexpected bioenergetic independent role of lactate as a signaling molecule necessary for mammalian eye morphogenesis.
巻・号 14(1)
ページ 4129
公開日 2023-7-14
DOI 10.1038/s41467-023-39672-2
PII 10.1038/s41467-023-39672-2
PMID 37452018
PMC PMC10349100
MeSH Animals Energy Metabolism Eye / metabolism Gene Expression Regulation Glycolysis / genetics Lactic Acid* / metabolism Mammals / metabolism Mice Morphogenesis / genetics Retina* / metabolism
IF 12.121
リソース情報
ヒト・動物細胞 Rx-GFP K/I EB5(AES0145)