在感染期间连接线粒体、脂肪酸和HSC扩张:对衰老和代谢疾病的影响。

IF 3.6 2区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
STEM CELLS Pub Date : 2025-07-29 DOI:10.1093/stmcls/sxaf053
Katherine Hampton, Alyssa Polski-Delve, Charlotte Hellmich, Stuart A Rushworth
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引用次数: 0

摘要

在稳定状态下,造血干细胞(hsc)安静地停留在低氧生态位中,线粒体活性最低,维持典型的低水平活性氧(ROS),转而倾向于糖酵解以满足其低能量需求。然而,压力,如急性感染,触发紧急造血状态,在此期间造血干细胞更快地扩增,产生多达10倍的下游分化免疫细胞。为了应对这种需求,造血干细胞通过从低atp产率的糖酵解转变为高atp产率的线粒体氧化磷酸化来增加其能量生产。正是这种代谢开关使HSC快速扩增并分化为下游后代,从而增加免疫细胞池并有效清除感染。这种代谢转换依赖于健康线粒体的充足可用性,以及以游离脂肪酸形式存在的燃料,以驱动细胞成分的必要生产。这篇简明的综述旨在关注HSC如何通过脂肪酸氧化增加其线粒体含量和燃料ATP的产生,以及在衰老和其他代谢疾病中HSC功能障碍的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Linking mitochondria, fatty acids and HSC expansion during infection: implications for aging and metabolic diseases.

In steady state, hematopoietic stem cells (HSCs) reside quiescently in their hypoxic niche with minimal mitochondrial activity, maintaining characteristically low levels of reactive oxygen species (ROS) and instead favoring glycolysis to meet their low energy requirements. However, stress, such as acute infection, triggers a state of emergency hematopoiesis during which HSCs expand more rapidly to produce up to ten-fold more downstream differentiated immune cells. To cope with this demand, HSCs increase their energy production by switching from low ATP-yielding glycolysis to high ATP-yielding mitochondrial oxidative phosphorylation. It is this metabolic switch that enables rapid HSC expansion and differentiation into downstream progeny to increase the immune cell pool and effectively clear the infection. This metabolic switch relies on the sufficient availability of healthy mitochondria as well as fuel in the form of free fatty acids to drive the necessary production of cellular components. This concise review aims to focus on how HSCs increase their mitochondrial content and fuel ATP production via fatty acid oxidation and the impact of HSC dysfunction during aging and other metabolic diseases.

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来源期刊
STEM CELLS
STEM CELLS 医学-生物工程与应用微生物
CiteScore
10.30
自引率
1.90%
发文量
104
审稿时长
3 months
期刊介绍: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. STEM CELLS is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. STEM CELLS covers: Cancer Stem Cells, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, Regenerative Medicine, Stem Cell Technology: Epigenetics, Genomics, Proteomics, and Metabonomics, Tissue-Specific Stem Cells, Translational and Clinical Research.
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