Single-Cell Metabolomics in Hematopoiesis and Hematological Malignancies.

Aberrant metabolism contributes to tumor initiation, progression, metastasis, and drug resistance. Metabolic dysregulation has emerged as a hallmark of several hematologic malignancies. Decoding the molecular mechanism underlying metabolic rewiring in hematological malignancies would provide promising avenues for novel therapeutic interventions. Single-cell metabolic analysis can directly offer a meaningful readout of the cellular phenotype, allowing us to comprehensively dissect cellular states and access biological information unobtainable from bulk analysis. In this review, we first highlight the unique metabolic properties of hematologic malignancies and underscore potential metabolic vulnerabilities. We then emphasize the emerging single-cell metabolomics techniques, aiming to provide a guide to interrogating metabolism at single-cell resolution. Furthermore, we summarize recent studies demonstrating the power of single-cell metabolomics to uncover the roles of metabolic rewiring in tumor biology, cellular heterogeneity, immunometabolism, and therapeutic resistance. Meanwhile, we describe a practical view of the potential applications of single-cell metabolomics in hematopoiesis and hematological malignancies. Finally, we present the challenges and perspectives of single-cell metabolomics development.