Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization.
Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization.
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DOI：
10.1016/j.jbc.2022.102418
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发表时间：
2022-10
影响因子：
4.8
通讯作者：
Zhang, Kangling
中科院分区：
文献类型：
--
作者：
Sowers, Mark L.;Tang, Hui;Singh, Vipul K.;Khan, Arshad;Mishra, Abhishek;Restrepo, Blanca I.;Jagannath, Chinnaswamy;Zhang, Kangling
巨噬细胞（Macrophages，M细胞）是一种重要的免疫细胞，用于防御和修复，可前往不同的组织并根据局部刺激进行适应。一个可能决定它们两极分化的关键因素是新陈代谢和表观遗传学之间的串扰。然而，同时测量代谢物、表观遗传学和蛋白质（表型）一直是一个重大的技术挑战。为了解决这个问题，我们开发了一种新的三组学方法，使用质谱法在单个样品中全面分析代谢物，蛋白质和组蛋白修饰。为了证明这一技术，我们研究了代谢表观遗传表型轴后极化的人血液来源的单核细胞成“促炎性M1-”或“抗炎性M2-”的M细胞。我们在这里报告精氨酸，色氨酸，葡萄糖和柠檬酸循环代谢，蛋白质和组蛋白翻译后修饰，和人巨噬细胞极化，以前没有描述之间的复杂关系。令人惊讶的是，M1-M β具有整体降低的组蛋白乙酰化水平，但具有高水平的乙酰化氨基酸。这表明乙酰辅酶A部分转向乙酰化氨基酸。与此相一致，葡萄糖的稳定同位素示踪显示M1-M β中用于组蛋白乙酰化的乙酰辅酶A的使用减少。此外，同位素示踪还揭示了从三羧酸循环中解偶联的糖酵解，如琥珀酸的同位素富集差所证明的。M2-M β具有高水平的犬尿氨酸和血清素，据报道具有免疫抑制作用。犬尿氨酸是NAD+从头代谢的上游，NAD+从头代谢是Sirtuin型组蛋白脱乙酰基酶的必要辅因子。总之，我们证明了代谢和表观遗传学之间复杂的相互作用，可能最终影响细胞表型。
Macrophages (MФ) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the crosstalk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) have been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, proteins, and histone modifications in a single sample. To demonstrate this technique, we investigated the metabolic-epigenetic-phenotype axis following polarization of human blood–derived monocytes into either ‘proinflammatory M1-’ or ‘anti-inflammatory M2-’ MФs. We report here a complex relationship between arginine, tryptophan, glucose, and the citric acid cycle metabolism, protein and histone post-translational modifications, and human macrophage polarization that was previously not described. Surprisingly, M1-MФs had globally reduced histone acetylation levels but high levels of acetylated amino acids. This suggests acetyl-CoA was diverted, in part, toward acetylated amino acids. Consistent with this, stable isotope tracing of glucose revealed reduced usage of acetyl-CoA for histone acetylation in M1-MФs. Furthermore, isotope tracing also revealed MФs uncoupled glycolysis from the tricarboxylic acid cycle, as evidenced by poor isotope enrichment of succinate. M2-MФs had high levels of kynurenine and serotonin, which are reported to have immune-suppressive effects. Kynurenine is upstream of de novo NAD+ metabolism that is a necessary cofactor for Sirtuin-type histone deacetylases. Taken together, we demonstrate a complex interplay between metabolism and epigenetics that may ultimately influence cell phenotype.
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影响因子：
64.5
作者：
Kaelin WG Jr;McKnight SL
通讯作者：
McKnight SL
影响因子：
5.5
作者：
Gessain G;Blériot C;Ginhoux F
通讯作者：
Ginhoux F
影响因子：
4
作者：
Frazão JB;Thain A;Zhu Z;Luengo M;Condino-Neto A;Newburger PE
通讯作者：
Newburger PE
DOI：
10.1016/j.numecd.2011.12.010
发表时间：
2012-05-01
影响因子：
3.9
作者：
Dall'Asta, M.;Derlindati, E.;Del Rio, D.
通讯作者：
Del Rio, D.
影响因子：
3.8
作者：
Baardman, Jeroen;Licht, Iris;Van den Bossche, Jan
通讯作者：
Van den Bossche, Jan