The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition.

ABSTRACT: Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1^-/- mouse embryos devoid of circulation the HSC lineage develops until the phenotypic pro-HSC stage. However, these cells reside in an abnormal microenvironment, fail to activate the hematopoietic program downstream of Runx1, and are functionally impaired. Single-cell transcriptomics shows that during the endothelial-to-hematopoietic transition, Ncx1^-/- cells fail to undergo a glycolysis to oxidative phosphorylation metabol

SUBMITTER: Azzoni E 

PROVIDER: S-EPMC8692754 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature