| First Author | Pv A | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 7 | Pages | eadh8478 |
| PubMed ID | 38363844 | Mgi Jnum | J:345408 |
| Mgi Id | MGI:7594982 | Doi | 10.1126/sciadv.adh8478 |
| Citation | Pv A, et al. (2024) Glycolytic state of aortic endothelium favors hematopoietic transition during the emergence of definitive hematopoiesis. Sci Adv 10(7):eadh8478 |
| abstractText | 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 effects on hematopoietic emergence. Conversely, stabilization of HIF-1alpha via inhibition of oxygen-sensing pathway led to decreased oxidative flux and promoted hematopoietic emergence in mid-gestation embryos. Thus, cell-intrinsic regulation of metabolic state overrides oxygenated microenvironment in the aorta to promote a glycolytic metabolic state that is crucial for hematopoietic emergence in mammalian embryos. |
