超越 ATP:作为红细胞分化调节器的代谢物网络

IF 5.3 2区 医学 Q1 PHYSIOLOGY Physiology Pub Date : 2024-09-03 DOI:10.1152/physiol.00035.2024
Axel Joly, Arthur Schott, Ira Phadke, Pedro Gonzalez-Menendez, Sandrina Kinet, Naomi Taylor
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引用次数: 0

摘要

造血干细胞(HSCs)具有自我更新和持续产生所有成熟血细胞系的能力。造血干细胞从自我更新状态向分化状态的转换是由新陈代谢线路控制的,这一点已得到公认,但直到最近,我们才认识到新陈代谢途径在调节祖细胞向不同造血系的承诺方面的重要性。在红细胞分化的过程中,红细胞(RBC)的成熟需要大量的代谢物,包括氨基酸、糖类、核苷酸、脂肪酸、维生素和铁。在这篇综述中,我们将重点介绍代谢物调节生理性红细胞生成的多方面作用,以及代谢紊乱对红细胞系的承诺和分化的影响。值得注意的是,红细胞分化过程与 SLC 代谢物转运体的广泛上调有关。最后,我们将讨论最近的研究如何揭示代谢重编程在红细胞生成障碍和无效疾病中的关键影响,从而为开发以代谢为中心的新型治疗策略创造机会。
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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.

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来源期刊
Physiology
Physiology 医学-生理学
CiteScore
14.50
自引率
0.00%
发文量
37
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.
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