The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments
Ricardo Grieshaber‐Bouyer, Felix A. Radtke, Pierre Cunin, Giuseppina Stifano, Anaïs Levescot, Brinda Vijaykumar, Nathan Nelson-Maney, Rachel B. Blaustein, Paul A. Monach, Peter A. Nigrović, Oscar A. Aguilar, Rhys S. Allan, Jilian Astarita, K. Frank Austen, Nora A. Barrett, Alev Baysoy, Christophe Benoıst, Brian D. Brown, Matthew B. Buechler, Jason D. Buenrostro, Maria Acebes Casanova, Kaitavjeet Chowdhary, Marco Colonna, Ty Crowl, Tianda Deng, Fiona Desland, Maxime Dhainaut, Jiarui Ding, Claudia X. Dominguez, Daniel F. Dwyer, Michela Frascoli, Shani T. Gal-Oz, Ananda W. Goldrath, Tim Johanson, Stefan Jordan, Joonsoo Kang, Varun Kapoor, Ephraim Kenigsberg, Joel Kim, Ki wook Kim, Evgeny Kiner, Mitchell Kronenberg, Lewis L. Lanier, Catherine Laplace, Caleb A. Lareau, Andrew M. Leader, Jisu Lee, Assaf Magen, Bárbara Maier, Alexandra Maslova, Diane Mathis, Adelle P. McFarland, M.S. Merad, Étienne Meunier, Paul A. Monach, Sara Mostafavi, Sören Müller, Christoph Muus, Hadas Ner‐Gaon, Quyhn Nguyen, Gherman Novakovsky, Stephen L. Nutt, Kayla Omilusik, Adriana Ortiz-Lopez, Mallory Paynich, Vincent Peng, Marc Potempa, Rachana Pradhan, Sara Quon, Ricardo N. Ramírez, Deepshika Ramanan, Gwendalyn J. Randolph, Aviv Regev, Samuel A. Rose, Kumba Seddu, Tal Shay, Avishai Shemesh, Justin A. Shyer, Christopher Smilie, Nick Spidale, Ayshwarya Subramanian, Katelyn Sylvia, Julie Tellier, Shannon J. Turley, Brinda Vijaykumar, Amy J. Wagers, Chendi Wang, Peter L. Wang, Aleksandra Wroblewska, Liang Yang, Aldrin Kay‐Yuen Yim, Hideyuki Yoshida
Abstract
Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal and inflamed mouse tissues. Whereas conventional clustering yields multiple alternative organizational structures, diffusion mapping plus RNA velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends from immature pre-neutrophils, largely in bone marrow, to mature neutrophils predominantly in blood and spleen. The sharpest increments in neutrotime occur during the transitions from pre-neutrophils to immature neutrophils and from mature marrow neutrophils to those in blood. Human neutrophils exhibit a similar transcriptomic pattern. Neutrophils migrating into inflamed mouse lung, peritoneum and joint maintain the core mature neutrotime signature together with new transcriptional activity that varies with site and stimulus. Together, these data identify a single developmental spectrum as the dominant organizational theme of neutrophil heterogeneity.