Daniela Cerezo‐Wallis, Andrea Rubio-Ponce, Mathis Richter, Emanuele Pitino, Immanuel Kwok, Giovanni Marteletto, Ana Cristina Guanolema-Coba, Changming Shih, Runkai Huang, Ana Moraga, Natalia Bravo, Samuel Doré, Sergio Callejas, David G. Aragonés, Daniel Jiménez‐Carretero, Daniel Martín-Pérez, Samuel Ovadia, Tommaso Vicanolo, Georgiana Crainiciuc, Jon Sicilia, Tong Deng, Anjelica Martin, Jing Zhang, María Isabel Cuartero, Diego Moncada Giraldo, Alicia García‐Culebras, Alejandra Aroca-Crevillén, Sandra Martín-Salamanca, Carlos Torroja, Max Ruiz, Irene Ruano, Melissa Ng, Jian Hou, You Wang, Mingyu Zhang, Jun Pu, Ana Herruzo, David Chang van Oordt, Seokyoon Chang, Alexander E. Downie, Fei Chen, Andrea L. Graham, William C. Gause, Pierre Fiset, Jonathan Spicer, Holger Heyn, María A. Zuriaga, Juan A. Bernal, Irina A. Udalova, Marı́a A. Moro, Katrien De Bock, Ana Dopazo, José J. Fuster, Fátima Sánchez‐Cabo, Juan C. Nieto, Gabriel F. Calvo, Julia Skokowa, Oliver Soehnlein, Daniela F. Quail, Logan A. Walsh, Lai Guan Ng, Andrés Hidalgo, Iván Ballesteros
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.