Features of lineage-specific hematopoietic metabolism revealed by mitochondrial proteomics.
Features of lineage-specific hematopoietic metabolism revealed by mitochondrial proteomics.
复制标题
线粒体蛋白质组学揭示谱系特异性造血代谢的特征。
DOI：
10.1002/pmic.201700053
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发表时间：
2017
期刊：
影响因子：
3.4
通讯作者：
Billing C
中科院分区：
文献类型：
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作者：
Billing C
造血骨髓是一种具有高度临床相关性的再生组织，但人们对相关干细胞和祖细胞群的代谢知之甚少。我们使用多能鼠细胞系来产生足够数量的细胞进行自我更新、红系或骨髓分化，以便对富集的线粒体进行蛋白质组学分析。严格的分析确定了 37 种线粒体相关蛋白在该系统中的分化过程中发生变化。分化过程中诱导的那些通常与成熟细胞功能相关，而分化过程中失活的那些则表明线粒体运输、脂肪酸分解代谢和氧化磷酸化的广泛变化。谷氨酸丙酮酸氨基转移酶 2 的红系特异性降低通过蛋白质印迹在蛋白质水平上得到证实，并通过代谢物周转分析在功能水平上得到证实。除了验证数据集之外，这些发现还表明红细胞生成和骨髓生成之间的核心代谢存在显着差异。这些知识与细胞治疗产品的体外生产以及再生组织中代谢和信号传导途径相互依赖性的研究相关。数据可通过 ProteomeXchange 获得，标识符为 PXD002968。
Hematopoietic bone marrow is a regenerative tissue of high clinical relevance, yet relatively little is known about the metabolism of the stem and progenitor populations concerned. We have used a multipotent murine cell line to generate sufficient numbers of cells undergoing self‐renewal, erythroid or myeloid differentiation to allow a proteomics analysis of enriched mitochondria. Stringent analysis identified 37 mitochondria‐associated proteins changing on differentiation in this system. Those induced during differentiation were commonly associated with mature cell functions, while those inactivated upon differentiation indicate widespread changes in mitochondrial transport, fatty acid catabolism and oxidative phosphorylation. An erythroid specific reduction in glutamate pyruvate amino transferase 2 was confirmed at the protein level by Western blotting and at the functional level by assays of metabolite turnover. In addition to validating the dataset, these findings suggest significant differences in the core‐metabolism between erythropoiesis and myelopoiesis. This knowledge is of relevance to the in vitro production of cell therapy products and to studies of the interdependence of metabolic and signaling pathways in regenerative tissues. Data are available via ProteomeXchange with identifier PXD002968.