A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease
Year: 2026
Type: article
Abstract: Neutrophils, the most abundant leukocytes in human blood, have multifaceted roles in health and disease. Here we assembled a single-cell atlas of human neutrophils (SCAHN) by integrating transcriptome data from 1 million human neutrophils from 781 samples and 43 independent datasets. Using SCAHN, we identified multiple neutrophil subsets with distinct functions across tissues and robust changes in gene expression and subset proportions in infection, cancer, immune suppression and sex differences at single-cell resolution. Cross-species reference mapping of mouse and nonhuman primate neutrophils onto SCAHN revealed both conserved and species-specific features. Using 17,023 bulk blood transcriptome profiles from 40 datasets, we found that neutrophil-specific signatures predicted mortality in acutely ill patients at presentation, were associated with cancer diagnosis and survival, and correlated with metabolic dysfunction and long-term all-cause mortality. Our study highlights how neutrophil biology can improve immune risk stratification and develop effective diagnostic and therapeutic strategies. Khatri and colleagues assembled a single-cell atlas of 1 million human neutrophils based on the integration of 43 independent single-cell transcriptome datasets to define multiple neutrophil subsets with distinct functions across tissues and disease states.
Source: Nature Immunology
Authors: Hong Zheng, Evan Maestri, Andrew R. Moore, Ananthakrishnan Ganesan, Jeanna Enriquez, Verónica Durán, Shirit Einav, Tom van der Poll, Hjalmar R. Bouma, Mihir R. Atreya, Philip A. Efron, Lyle L. Moldawer, Jonathan Sevransky, David W. Wright, Ignacio Martin-Loeches, Thomas Karvunidis, Jeremiah Hinson, David N. Hager, Richard E. Rothman, Evangelos J. Giamarellos-Bourboulis, Timothy E. Sweeney, Angela J. Rogers, Saurabh Gombar, Manoj V. Maddali, Jonathan H. Chen, Nigam Shah, Purvesh Khatri
Institutions: Stanford Medicine, Stanford University, Chan Zuckerberg Biohub San Francisco, Amsterdam University Medical Centers, University of Amsterdam, University Medical Center Groningen, University of Groningen, Cincinnati Children's Hospital Medical Center, University of Cincinnati, University of Florida Health, University of Florida, Emory University, Trinity College Dublin, St. James's Hospital, Charles University, Johns Hopkins University, Danaher (United States), National and Kapodistrian University of Athens, Hellenic Institute for the Study of Sepsis, Piedmont Atlanta Hospital, Stanford Health Care
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Bill and Melinda Gates Foundation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Stanford Bio-X, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: Stanford University - To continue a center for human immunological analysis that can drive projects with the goal of improving the design and delivery of global health v..., Stanford University - to establish a state-of-the-art center for immunological analysis at Stanford University, with the goal of accelerating global health and vaccine r..., Stanford University - to build computational foundational models of human immunology optimized for global health, G73616645, Stanford Center for Clinical and Translational Research and Education, Understanding Influenza and SARS-CoV-2 vaccine responses, in vivo and in vitro, Stanford Training Program in Lung Biology, Systems biological assessment of innate and adaptive immunity to vaccination, Molecular and Cellular Immunobiology, Measuring and Predicting Appropriate Antibiotic Use to Combat Resistant Bacteria
OpenAlex ID: W7223140000