Fueling fate: Metabolic crosstalk in the bone marrow microenvironment

The bone marrow (BM) serves as the principal site of blood production in adults. The BM's remarkable ability to maintain and regenerate the entire hematopoietic system is built upon an intricate cellular composition that coordinately responds and adapts to organismal demands. Within this specialized multicellular microenvironment, commonly referred to as “niche,” intercellular communication plays a pivotal role in maintaining proper tissue function. In this review, we focus on an important, yet often-overlooked regulatory mechanism: the metabolic crosstalk in the BM microenvironment. Metabolic cues have emerged as key regulators of hematopoietic stem cell (HSC) fate decisions. Consequently, the tight regulation of BM niche metabolism is increasingly being recognized as a key player in tissue homeostasis. Moreover, BM niche metabolic crosstalk is frequently altered in disease, contributes to pathogenesis and influences treatment outcomes. By providing a comprehensive overview of the metabolic interplay in the BM microenvironment during health and disease, this chapter seeks to highlight its potential for identifying new therapeutic targets and developing strategies to ameliorate disease outcomes.