巨噬细胞是效应免疫细胞，在穿过组织时，特别是在进入肿瘤或感染伤口时，氧合会发生巨大变化。缺氧如何在转录后水平改变基因表达和巨噬细胞效应功能仍知之甚少。在这里，我们使用 TimeLapse-seq 来测量炎症激活如何改变原代巨噬细胞的缺氧反应。核苷重新编码测序可以从同一数据集推导出稳态转录水平、降解率和转录合成率。我们发现缺氧会引起静息巨噬细胞和炎症巨噬细胞的不同反应。缺氧会导致 mRNA 转录物不稳定，但与静息巨噬细胞相比，炎症巨噬细胞会显着增加 mRNA 降解。 RNA 周转增加导致核糖体蛋白基因上调和炎症巨噬细胞中细胞外基质成分下调。体外 mRNA 衰变调节的通路在肿瘤相关巨噬细胞中受到差异性调节，这意味着混合刺激可以诱导实体瘤中巨噬细胞功能的转录后调节。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Macrophages are effector immune cells that experience substantial changes to oxygenation when transiting through tissues, especially when entering tumors or infected wounds. How hypoxia alters gene expression and macrophage effector function at the post-transcriptional level remains poorly understood. Here, we use TimeLapse-seq to measure how inflammatory activation modifies the hypoxic response in primary macrophages. Nucleoside recoding sequencing allows the derivation of steady-state transcript levels, degradation rates, and transcriptional synthesis rates from the same dataset. We find that hypoxia produces distinct responses from resting and inflammatory macrophages. Hypoxia induces destabilization of mRNA transcripts, though inflammatory macrophages substantially increase mRNA degradation compared to resting macrophages. Increased RNA turnover results in the upregulation of ribosomal protein genes and downregulation of extracellular matrix components in inflammatory macrophages. Pathways regulated by mRNA decay in vitro are differentially regulated in tumor-associated macrophages implying that mixed stimuli could induce post-transcriptional regulation of macrophage function in solid tumors.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.