Metabolite patterns in human myeloid hematopoiesis result from lineage-dependent active metabolic pathways

Abstract

Assessment of hematotoxicity from environmental or xenobiotic compounds is of notable interest and is frequently assessed via the colony forming unit (CFU) assay. Identification of the mode of action of single compounds is of further interest, as such often enables transfer of results across different tissues and compounds. Metabolomics displays one promising approach for identifying such, nevertheless, suitability with current protocols is restricted. Here, we combined an HSPC expansion approach with distinct lineage differentiations, resulting in formation of erythrocytes, dendritic cells and neutrophils. We examined the unique combination of fluxes in glycolysis, glutaminolysis, polyamine synthesis, fatty acid oxidation and synthesis, as well as glycerophospholipid and sphingolipid metabolism. We further assessed their interconnections and essentialness for each lineage formation. By this, we provide further insights into metabolic fluxes during differentiation of HSPC into different lineages, enabling profound understanding of possible metabolic changes in each lineage caused by exogenous compounds.