Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
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DOI：
10.1016/j.immuni.2014.01.006
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发表时间：
2014-02-20
期刊：
影响因子：
32.4
通讯作者：
Schultze, Joachim L.
中科院分区：
文献类型：
--
作者：
Xue, Jia;Schmidt, Susanne V.;Sander, Jil;Draffehn, Astrid;Krebs, Wolfgang;Quester, Inga;De Nardo, Dominic;Gohel, Trupti D.;Emde, Martina;Schmidleithner, Lisa;Ganesan, Hariharasudan;Nino-Castro, Andrea;Mallmann, Michael R.;Labzin, Larisa;Theis, Heidi;Kraut, Michael;Beyer, Marc;Latz, Eicke;Freeman, Tom C.;Ulas, Thomas;Schultze, Joachim L.
巨噬细胞的激活与深刻的转录重编程有关。虽然在理解巨噬细胞的激活、极化和功能方面已经取得了很大进展，但调节这些过程的转录程序仍然缺乏特征性。我们用不同的激活信号刺激人巨噬细胞，获得了299个巨噬细胞转录本的数据集。对这一数据集的分析揭示了巨噬细胞激活状态的频谱，扩展了当前的M1与M2极化模型。网络分析确定了与所有巨噬细胞激活相关的中央转录调控因子，并辅之以与刺激特异性程序相关的调控因子。将这些转录程序应用于吸烟者和慢性阻塞性肺疾病(COPD)患者的人肺泡巨噬细胞，发现COPD患者意外地失去了炎症特征。最后，通过整合来自ImmGen项目的小鼠数据，我们为人和小鼠巨噬细胞提出了一个精炼的、不依赖于激活的核心签名。这一资源为未来研究巨噬细胞激活在健康和疾病中的调控提供了一个框架。巨噬细胞对不同信号的特异性转录程序反应被肿瘤坏死因子、前列腺素E_2和P3C激活激活STAT4相关转录程序NFKB1、JunB和CREB1是巨噬细胞激活的中心转录因子COPD患者肺泡巨噬细胞炎性信号丢失
Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization, and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a data set of 299 macrophage transcriptomes. Analysis of this data set revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease. Macrophages react with specific transcriptional programming upon distinct signals Activation by TNF, PGE2, and P3C activates a STAT4-associated transcriptional program NFKB1, JUNB, and CREB1 are central transcription factors of macrophage activation Inflammatory signatures are lost in alveolar macrophages from COPD patients
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作者：
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