[Metabolic regulation for cell fate decision of hematopoietic stem cells]

Stem cells are self-renewing, either multipotent or unipotent, and they offer opportunities for stem cell-based therapies in the clinical setting. The mechanism underlying the division patterns of hematopoietic stem cells (HSCs) is one of the most fundamental biological questions. However, to date, analyses of individual HSC cell fate decisions have been restricted by the heterogeneity of available HSC-enriched fractions and the technical challenges of imaging HSC fate. Comprehensive research accompanied with genetic models, metabolomics analyses, and single-cell approaches have highlighted the critical contributions of metabolic control to HSC homeostasis. Consequently, the roles of mitochondrial metabolism in the HSC division symmetry have become a central focus of the current research. Nevertheless, we are only beginning to comprehend the metabolic requirements of stemness. This review summarizes the recent advances in our understanding of the intriguing relationship between mitochondrial metabolism and HSC fate decisions. In addition, this study highlights our recent findings regarding the contributions of the mitochondrial quality control by autophagy to HSC division balance. Elucidation of the metabolic cues governing HSC fate decisions should lead to new techniques of metabolic manipulation, which can shift the division balance of HSCs and offer effective targets in strategies against leukemia and will, thus, be of high clinical importance.