Glycolytic state of aortic endothelium favors hematopoietic transition during the emergence of definitive hematopoiesis.

ABSTRACT: The first definitive hematopoietic progenitors emerge through the process of endothelial-to-hematopoietic transition in vertebrate embryos. With molecular regulators for this process worked out, the role of metabolic pathways used remains unclear. Here, we performed nano-LC-MS/MS-based proteomic analysis and predicted a metabolic switch from a glycolytic to oxidative state upon hematopoietic transition. Mitochondrial activity, glucose uptake, and glycolytic flux analysis supported this hypothesis. Systemic inhibition of lactate dehydrogenase A (LDHA) increased oxygen consumption rate in the hemato-endothelial system and inhibited the emergence of intra-aortic hematopoietic clusters. These findings were corroborated using Tie2-Cre-mediated deletion of Ldha that showed similar

SUBMITTER: Pv A 

PROVIDER: S-EPMC10871539 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature