Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages.
Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages.
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胚胎来源和成年来源的巨噬细胞具有明显的缺氧诱导的翻译图谱。
DOI：
10.1016/j.isci.2023.107985
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发表时间：
2023-12-15
期刊：
影响因子：
5.8
通讯作者：
Bender, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Wilcox, Nicholas S.;Yarovinsky, Timur O.;Pandya, Prakruti;Ramgolam, Vinod S.;Moro, Albertomaria;Wu, Yinyu;Nicoli, Stefania;Hirschi, Karen K.;Bender, Jeffrey R.
组织驻留巨噬细胞主要来源于胚胎（胎肝）且寿命较长，而骨髓来源的巨噬细胞（BMDM）在急性扰动（如心肌缺血情况下的缺氧）后被募集。先前的转录组分析在RNA表达水平上确定了BMDM和胎肝来源巨噬细胞（FLDM）的差异。决定mRNA稳定性和翻译速率的转录后调控可能会覆盖对缺氧的转录信号。我们在mRNA翻译水平上分析了对缺氧有差异调节的BMDM和FLDM转录本。利用翻译核糖体亲和纯化（TRAP）分析和RNA - seq，我们鉴定出在缺氧后BMDM（Ly6e、波形蛋白、PF4）和FLDM（Ccl7、Ccl2）中翻译速率增加的非重叠转录本。我们进一步在这些亚群中鉴定出受RNA结合蛋白HuR调控的缺氧诱导转录本。这些发现明确了巨噬细胞亚群基因表达程序的翻译差异，突出了缺血心肌中潜在的治疗靶点。
缺氧改变BMDM和FLDM中总多聚（A）RNA和翻译的多聚（A）RNA的图谱
缺氧调节BMDM和FLDM中不同的免疫和代谢调节因子
RNA结合蛋白HuR改变巨噬细胞对缺氧和组织损伤的反应
生物科学；分子生物学；免疫学；细胞生物学
Tissue resident macrophages are largely of embryonic (fetal liver) origin and long-lived, while bone marrow–derived macrophages (BMDM) are recruited following an acute perturbation, such as hypoxia in the setting of myocardial ischemia. Prior transcriptome analyses identified BMDM and fetal liver–derived macrophage (FLDM) differences at the RNA expression level. Posttranscriptional regulation determining mRNA stability and translation rate may override transcriptional signals in response to hypoxia. We profiled differentially regulated BMDM and FLDM transcripts in response to hypoxia at the level of mRNA translation. Using a translating ribosome affinity purification (TRAP) assay and RNA-seq, we identified non-overlapping transcripts with increased translation rate in BMDM (Ly6e, vimentin, PF4) and FLDM (Ccl7, Ccl2) after hypoxia. We further identified hypoxia-induced transcripts within these subsets that are regulated by the RNA-binding protein HuR. These findings define translational differences in macrophage subset gene expression programs, highlighting potential therapeutic targets in ischemic myocardium. Hypoxia alters profiles of total and translated poly(A) RNA in BMDM and FLDM Hypoxia regulates different immune and metabolic regulators in BMDM and FLDM RNA-binding protein HuR modifies macrophage responses to hypoxia and tissue injury Biological sciences; Molecular biology; Immunology; Cell biology
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