Pyruvate Metabolism Guides Definitive Lineage Specification During Hematopoietic Emergence

ABSTRACT: During embryonic development, hematopoiesis occurs through primitive and definitive waves, giving rise to distinct blood lineages. Hematopoietic stem cells (HSCs) emerge from hemogenic endothelial (HE) cells, through endothelial to hematopoietic transition (EHT). In the adult, HSC quiescence, maintenance and differentiation are closely linked to changes in metabolism. However, metabolic processes underlying the emergence of HSCs from HE cells remain unclear. Here we show that the emergence of blood is regulated by multiple metabolic pathways that induce or modulate the differentiation towards specific hematopoietic lineages during human EHT. In both in vitro and in vivo settings, steering pyruvate use towards glycolysis or OXPHOS differentially skews the hematopoietic output of HE cells to

SUBMITTER: Dr. Leal Oburoglu 

PROVIDER: S-SCDT-EMBOR-2021-54384-T | biostudies-other |

REPOSITORIES: biostudies-other