Metabolism and metabolites regulating hematopoiesis

Energy metabolism of immune cells, such as glycolysis and mitochondrial activity, requires strict regulation. This is especially critical in the complex environment of the bone marrow (BM), where there is a need to both preserve the quiescence of hematopoietic stem cells (HSCs) and guarantee timed and effective lineage differentiation of the HSCs. Recent advances highlight the critical roles played by bioactive metabolites in regulating hematopoiesis. In particular, secreted immune metabolites (SIMets), such as γ-aminobutyric acid (GABA) and acetylcholine, secreted by B-lineage cells, act as potent modulators of hematopoietic processes, influencing HSC differentiation and emergency hematopoiesis. In this review, we provide an overview and discuss mechanisms by which energy metabolism and SIMets regulate hematopoiesis. We propose that biochemical communication facilitated by these metabolites is essential for maintaining the BM niche and suggest potential therapeutic strategies using SIMets in hematological disorders.