Axel Joly, Arthur Schott, Ira Phadke, Pedro Gonzalez-Menendez, Sandrina Kinet, Naomi Taylor
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Beyond ATP: Metabolite networks as regulators of erythroid differentiation.
Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and the sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls the switch of HSCs from a self-renewal state to a more differentiated state but it is only recently that we have appreciated the importance of metabolic pathways in regulating the commitment of progenitors to distinct hematopoietic lineages. In the context of erythroid differentiation, an extensive network of metabolites - including amino acids, sugars, nucleotides, fatty acids, vitamins, and iron - is required for red blood cell (RBC) maturation. In this review, we will highlight the multi-faceted roles via which metabolites regulate physiological erythropoiesis as well as the effects of metabolic perturbations on erythroid lineage commitment and differentiation. Of note, the erythroid differentiation process is associated with an exceptional breadth of SLC metabolite transporter upregulation. Finally, we will discuss how recent research, revealing the critical impact of metabolic reprogramming in diseases of disordered and ineffective erythropoiesis, has created opportunities for the development of novel metabolic-centered therapeutic strategies.
期刊介绍:
Physiology journal features meticulously crafted review articles penned by esteemed leaders in their respective fields. These articles undergo rigorous peer review and showcase the forefront of cutting-edge advances across various domains of physiology. Our Editorial Board, comprised of distinguished leaders in the broad spectrum of physiology, convenes annually to deliberate and recommend pioneering topics for review articles, as well as select the most suitable scientists to author these articles. Join us in exploring the forefront of physiological research and innovation.