Abstract
The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.
摘要
低温对健康的负面影响容易诱发多种疾病,因此我们试图通过研究冷暴露后巨噬细胞微调的机制来了解冷应激诱发疾病的原因。在本研究中,我们发现冷应激会引发巨噬细胞活化增加,并伴随有氧糖酵解的代谢重编程,而且冷暴露后的线粒体缺陷可能有助于这一过程。全基因组RNA测序的结果进一步确定了冷暴露后小鼠巨噬细胞中的线粒体缺陷。此外,新陈代谢的变化通过影响组蛋白修饰来驱动巨噬细胞的分化。最后,我们发现组蛋白乙酰化和乳酸化是冷暴露后巨噬细胞分化的调节剂。总而言之,代谢相关的表观遗传修饰对于冷应激小鼠巨噬细胞的分化至关重要,而代谢调控可能有助于减轻冷应激的危害。
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This work was supported by the National Natural Science Foundation of China (Nos. 31672513 and 31772695), the Heilongjiang Provincial Natural Science Foundation of China (No. YQ2021C027), the Key Program of Natural Science Foundation of Heilongjiang Province (No. ZD2019C004), and the Heilongjiang Bayi Agricultural University for San Heng San Zong (No. ZRCQC202003), China.
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Conceptualization: Bin XU and Jingru GUO; Writing original draft, review and editing, data curation, and formal analysis: Jingjing LU and Shoupeng FU; Funding acquisition: Shize LI, Bin XU, and Huanmin YANG; Investigation: Jie DAI, Jianwen HU, Hong JI, Jiahong YU, and Jiming BAO; Methodology: Zhiquan WANG; Supervision: Bin XU and Jingru GUO.
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Jingjing LU, Shoupeng FU, Jie DAI, Jianwen HU, Shize LI, Hong JI, Zhiquan WANG, Jiahong YU, Jiming BAO, Bin XU, Jingru GUO, and Huanmin YANG declare that they have no conflict of interest.
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Lu, J., Fu, S., Dai, J. et al. Integrated metabolism and epigenetic modifications in the macrophages of mice in responses to cold stress. J. Zhejiang Univ. Sci. B 23, 461–480 (2022). https://doi.org/10.1631/jzus.B2101091
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DOI: https://doi.org/10.1631/jzus.B2101091