卡洛斯三世国家心血管研究中心Iván Ballesteros团队宣布他们揭示了中性粒细胞室的结构。这一研究成果发表在2025年12月3日出版的国际学术期刊《自然》上。

在这里，该研究组对中性粒细胞进行了跨越47种解剖、生理和病理情况的单细胞转录谱分析，以生成小鼠全球中性粒细胞区室的综合图，该研究组称之为NeuMap。NeuMap集成并扩展了现有模型，以产生基本的新见解；它揭示了中性粒细胞在有限数量的功能枢纽中组织，这些功能枢纽在成熟过程中依次分布，然后分支到干扰素应答和免疫抑制状态，以及在健康循环中占主导地位的功能沉默状态。计算模型和时间戳分析确定了连接这些中心的原型轨迹，并揭示了在健康、炎症和癌症期间的动态和首选路径的变化。

研究人员发现，TGFβ、IFNβ和GM-CSF沿不同的轨迹影响中性粒细胞，并将染色质可及性位点投射到NeuMap上，表明转录因子JUNB控制血管生成和免疫抑制状态，促进组织血运重建。NeuMap的结构似乎在性别、环境和遗传背景以及人类中都是保守的。最后，课题组人员发现NeuMap可以通过分析血液中性粒细胞来推断宿主的病理生理状态。他们的研究描绘了中性粒细胞区室的整体结构，并为探索和利用中性粒细胞生物学建立了框架。

据悉，中性粒细胞在不同组织和疾病中表现出显著的表型和功能多样性，但缺乏对这种免疫区是如何在全球组织的理解，这给临床应用带来了挑战。

附：英文原文

Title: Architecture of the neutrophil compartment

Author: Cerezo-Wallis, Daniela, Rubio-Ponce, Andrea, Richter, Mathis, Pitino, Emanuele, Kwok, Immanuel, Marteletto, Giovanni, Guanolema-Coba, Ana Cristina, Shih, Changming, Huang, Run-Kai, Moraga, Ana, Bravo, Natalia Borbaran, Dor, Samuel, Callejas, Sergio, Aragons, David G., Jimnez-Carretero, Daniel, Martin, Daniel, Ovadia, Samuel, Vicanolo, Tommaso, Crainiciuc, Georgiana, Sicilia, Jon, Deng, Tong, Martin, Anjelica, Zhang, Jing, Cuartero, Maria Isabel, Giraldo, Diego Moncada, Garcia-Culebras, Alicia, Aroca-Crevillen, Alejandra, Martn-Salamanca, Sandra, Torroja, Carlos, Ruiz, Max, Ruano, Irene, Ng, Melissa S. F., Hou, Jian, Wang, You, Zhang, Ming, Pu, Jun, Herruzo, Ana, van Oordt, David Chang, Chang, Seokyoon, Downie, Alexander E., Chen, Fei, Graham, Andrea L., Gause, William C., Fiset, Pierre O., Spicer, Jonathan D., Heyn, Holger, Zuriaga, Maria A., Bernal, Juan A., Udalova, Irina A., Moro, Maria A., de Bock, Katrien, Dopazo, Ana, Fuster, Jose J., Snchez-Cabo, Ftima, Nieto, Juan C., Calvo, Gabriel F., Skokowa, Julia, Soehnlein, Oliver, Quail, Daniela F., Walsh, Logan A., Ng, Lai Guan, Hidalgo, Andrs, Ballesteros, Ivn

Issue&Volume: 2025-12-03

Abstract: Neutrophils exhibit remarkable phenotypic and functional diversity across tissues and diseases1,2, yet the lack of understanding of how this immune compartment is globally organized challenges translation to the clinic. Here we performed single-cell transcriptional profiling of neutrophils spanning 47 anatomical, physiological and pathological scenarios to generate an integrated map of the global neutrophil compartment in mice, which we refer to as NeuMap. NeuMap integrates and expands existing models3,4 to generate fundamental new insights; it reveals that neutrophils organize in a finite number of functional hubs that distribute sequentially during maturation to then branch out into interferon-responsive and immunosuppressive states, as well as a functionally silent state that dominates in the healthy circulation. Computational modelling and timestamp analyses identify prototypical trajectories that connect these hubs, and reveal that the dynamics and preferred paths vary during health, inflammation and cancer. We show that TGFβ, IFNβ and GM-CSF push neutrophils along the different trajectories, and projection of chromatin accessibility sites onto NeuMap reveals that the transcription factor JUNB controls angiogenic and immunosuppressive states and promotes tissue revascularization. The architecture of NeuMap appears to be conserved across sex, environmental and genetic backgrounds, as well as in humans. Finally, we show that NeuMap enables inference of the pathophysiological state of the host by profiling blood neutrophils. Our study delineates the global architecture of the neutrophil compartment and establishes a framework for exploration and exploitation of neutrophil biology.

DOI: 10.1038/s41586-025-09807-0

Source: https://www.nature.com/articles/s41586-025-09807-0