---
title: "Single-cell atlas SCAHN maps human neutrophil heterogeneity across health and disease"
id: "nature-immunology-1-a-single-cell-atlas-of-human-neutrophils-reveals-neutrophil-heterogeneity"
canonical_url: "https://medichelpline.com/clinical-feed/nature-immunology-1-a-single-cell-atlas-of-human-neutrophils-reveals-neutrophil-heterogeneity"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Nature Immunology"
source_url: "https://www.nature.com/articles/s41590-026-02671-8"
published_at: "2026-10-21T12:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Single-cell atlas SCAHN maps human neutrophil heterogeneity across health and disease
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/nature-immunology-1-a-single-cell-atlas-of-human-neutrophils-reveals-neutrophil-heterogeneity
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Nature Immunology
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41590-026-02671-8)
- **Published At:** 2026-10-21T12:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The study assembled a single-cell atlas of human neutrophils (**SCAHN**) by integrating transcriptomes from 1 million neutrophils drawn from 781 samples and 43 independent scRNA-seq datasets. - Investigators combined data across seven sequencing platforms, nine countries and more than 20 tissues, including peripheral blood, cord blood, bone marrow, lung, liver, colorectum, pancreas and spleen. - The cohort included healthy donors and patients with infection, lung cancer, cardiovascular disease, autoimmune disorders and other conditions; median neutrophil proportions varied by sample type and platform. - Clustering of integrated data identified multiple transcriptionally distinct neutrophil subsets with tissue-specific distributions and functional annotations revealed by gene-expression patterns. - The atlas captured robust changes in neutrophil gene expression and subset proportions linked to infection severity, cancer, immune suppression and sex differences at single-cell resolution. - Cross-species mapping projected mouse and nonhuman primate neutrophils onto SCAHN, revealing both conserved and species-specific features; the source reported these comparisons but did not detail specific conserved markers in this summary. - Authors defined neutrophil-specific transcriptomic signatures from SCAHN and quantified those signatures in 17,023 bulk blood transcriptomes, finding associations with mortality in acutely ill patients, cancer diagnosis and survival, metabolic dysfunction, and long-term all-cause mortality. - Two clinical cohorts comprising over 430,000 electronic health records were used to analyze links between neutrophil-associated signatures and higher risk of chronic disease and all-cause mortality. - The source emphasized that prior scRNA-seq studies used varied protocols and nomenclature; the integrated atlas aims to harmonize neutrophil subset definitions across diverse conditions and tissues. - The paper provides a resource for cross-study comparison, diagnostics and potential therapeutic targeting, while the authors noted the need for continued standardization and further functional validation of identified subsets.
## Clinical Analysis & Structured Key Points
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[resources](https://www.nature.com/ni/articles?type=resource) 4. article A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease [ Download PDF ](https://www.nature.com/articles/s41590-026-02671-8.pdf) [ Download PDF ](https://www.nature.com/articles/s41590-026-02671-8.pdf) * Resource * [Open access](https://www.springernature.com/gp/open-science/about/the-fundamentals-of-open-access-and-open-research) * Published: 21 October 2026 # A single-cell atlas of human neutrophils reveals neutrophil heterogeneity across health and disease * [Hong Zheng](https://www.nature.com/articles/s41590-026-02671-8#auth-Hong-Zheng-Aff1-Aff2) [ORCID: orcid.org/0000-0002-8884-8211](https://orcid.org/0000-0002-8884-8211)[1](https://www.nature.com/articles/s41590-026-02671-8#Aff1),[2](https://www.nature.com/articles/s41590-026-02671-8#Aff2), * [Evan Maestri](https://www.nature.com/articles/s41590-026-02671-8#auth-Evan-Maestri-Aff3) [ORCID: orcid.org/0000-0003-4829-1444](https://orcid.org/0000-0003-4829-1444)[3](https://www.nature.com/articles/s41590-026-02671-8#Aff3), * [Andrew R. Moore](https://www.nature.com/articles/s41590-026-02671-8#auth-Andrew_R_-Moore-Aff4) [ORCID: orcid.org/0000-0001-8040-2576](https://orcid.org/0000-0001-8040-2576)[4](https://www.nature.com/articles/s41590-026-02671-8#Aff4), * [Ananthakrishnan Ganesan](https://www.nature.com/articles/s41590-026-02671-8#auth-Ananthakrishnan-Ganesan-Aff1-Aff2)[1](https://www.nature.com/articles/s41590-026-02671-8#Aff1),[2](https://www.nature.com/articles/s41590-026-02671-8#Aff2), * [Jeanna Enriquez](https://www.nature.com/articles/s41590-026-02671-8#auth-Jeanna-Enriquez-Aff3)[3](https://www.nature.com/articles/s41590-026-02671-8#Aff3), * [Verónica Durán](https://www.nature.com/articles/s41590-026-02671-8#auth-Ver_nica-Dur_n-Aff5)[5](https://www.nature.com/articles/s41590-026-02671-8#Aff5), * [Shirit Einav](https://www.nature.com/articles/s41590-026-02671-8#auth-Shirit-Einav-Aff5-Aff6-Aff7) [ORCID: orcid.org/0000-0001-6441-4171](https://orcid.org/0000-0001-6441-4171)[5](https://www.nature.com/articles/s41590-026-02671-8#Aff5),[6](https://www.nature.com/articles/s41590-026-02671-8#Aff6),[7](https://www.nature.com/articles/s41590-026-02671-8#Aff7), * [Tom van der Poll](https://www.nature.com/articles/s41590-026-02671-8#auth-Tom-Poll-Aff8-Aff9) [ORCID: orcid.org/0000-0002-9199-5079](https://orcid.org/0000-0002-9199-5079)[8](https://www.nature.com/articles/s41590-026-02671-8#Aff8),[9](https://www.nature.com/articles/s41590-026-02671-8#Aff9), * [Hjalmar R. Bouma](https://www.nature.com/articles/s41590-026-02671-8#auth-Hjalmar_R_-Bouma-Aff10-Aff11-Aff12)[10](https://www.nature.com/articles/s41590-026-02671-8#Aff10),[11](https://www.nature.com/articles/s41590-026-02671-8#Aff11),[12](https://www.nature.com/articles/s41590-026-02671-8#Aff12), * [Mihir R. Atreya](https://www.nature.com/articles/s41590-026-02671-8#auth-Mihir_R_-Atreya-Aff13)[13](https://www.nature.com/articles/s41590-026-02671-8#Aff13), * [Philip A. Efron](https://www.nature.com/articles/s41590-026-02671-8#auth-Philip_A_-Efron-Aff14)[14](https://www.nature.com/articles/s41590-026-02671-8#Aff14), * [Lyle L. Moldawer](https://www.nature.com/articles/s41590-026-02671-8#auth-Lyle_L_-Moldawer-Aff14)[14](https://www.nature.com/articles/s41590-026-02671-8#Aff14), * [Jonathan Sevransky](https://www.nature.com/articles/s41590-026-02671-8#auth-Jonathan-Sevransky-Aff15)[15](https://www.nature.com/articles/s41590-026-02671-8#Aff15), * [David W. Wright](https://www.nature.com/articles/s41590-026-02671-8#auth-David_W_-Wright-Aff16) [ORCID: orcid.org/0000-0002-7145-9105](https://orcid.org/0000-0002-7145-9105)[16](https://www.nature.com/articles/s41590-026-02671-8#Aff16), * [Ignacio Martin-Loeches](https://www.nature.com/articles/s41590-026-02671-8#auth-Ignacio-Martin_Loeches-Aff17-Aff18)[17](https://www.nature.com/articles/s41590-026-02671-8#Aff17),[18](https://www.nature.com/articles/s41590-026-02671-8#Aff18), * [Thomas Karvunidis](https://www.nature.com/articles/s41590-026-02671-8#auth-Thomas-Karvunidis-Aff19)[19](https://www.nature.com/articles/s41590-026-02671-8#Aff19), * [Jeremiah Hinson](https://www.nature.com/articles/s41590-026-02671-8#auth-Jeremiah-Hinson-Aff20-Aff21)[20](https://www.nature.com/articles/s41590-026-02671-8#Aff20),[21](https://www.nature.com/articles/s41590-026-02671-8#Aff21), * [David N. Hager](https://www.nature.com/articles/s41590-026-02671-8#auth-David_N_-Hager-Aff22)[22](https://www.nature.com/articles/s41590-026-02671-8#Aff22), * [Richard E. Rothman](https://www.nature.com/articles/s41590-026-02671-8#auth-Richard_E_-Rothman-Aff20)[20](https://www.nature.com/articles/s41590-026-02671-8#Aff20), * [Evangelos J. Giamarellos-Bourboulis](https://www.nature.com/articles/s41590-026-02671-8#auth-Evangelos_J_-Giamarellos_Bourboulis-Aff23-Aff24) [ORCID: orcid.org/0000-0003-4713-3911](https://orcid.org/0000-0003-4713-3911)[23](https://www.nature.com/articles/s41590-026-02671-8#Aff23),[24](https://www.nature.com/articles/s41590-026-02671-8#Aff24), * [Timothy E. Sweeney](https://www.nature.com/articles/s41590-026-02671-8#auth-Timothy_E_-Sweeney-Aff25) [ORCID: orcid.org/0000-0002-3596-1093](https://orcid.org/0000-0002-3596-1093)[25](https://www.nature.com/articles/s41590-026-02671-8#Aff25), * [Angela J. Rogers](https://www.nature.com/articles/s41590-026-02671-8#auth-Angela_J_-Rogers-Aff4) [ORCID: orcid.org/0000-0001-6969-6200](https://orcid.org/0000-0001-6969-6200)[4](https://www.nature.com/articles/s41590-026-02671-8#Aff4), * [Saurabh Gombar](https://www.nature.com/articles/s41590-026-02671-8#auth-Saurabh-Gombar-Aff26)[26](https://www.nature.com/articles/s41590-026-02671-8#Aff26), * [Manoj V. Maddali](https://www.nature.com/articles/s41590-026-02671-8#auth-Manoj_V_-Maddali-Aff27)[27](https://www.nature.com/articles/s41590-026-02671-8#Aff27), * [Jonathan H. Chen](https://www.nature.com/articles/s41590-026-02671-8#auth-Jonathan_H_-Chen-Aff2-Aff28-Aff29)[2](https://www.nature.com/articles/s41590-026-02671-8#Aff2),[28](https://www.nature.com/articles/s41590-026-02671-8#Aff28),[29](https://www.nature.com/articles/s41590-026-02671-8#Aff29), * [Nigam Shah](https://www.nature.com/articles/s41590-026-02671-8#auth-Nigam-Shah-Aff2-Aff29-Aff30) [ORCID: orcid.org/0000-0001-9385-7158](https://orcid.org/0000-0001-9385-7158)[2](https://www.nature.com/articles/s41590-026-02671-8#Aff2),[29](https://www.nature.com/articles/s41590-026-02671-8#Aff29),[30](https://www.nature.com/articles/s41590-026-02671-8#Aff30) & * … * [Purvesh Khatri](https://www.nature.com/articles/s41590-026-02671-8#auth-Purvesh-Khatri-Aff1-Aff2) [ORCID: orcid.org/0000-0002-4143-4708](https://orcid.org/0000-0002-4143-4708)[1](https://www.nature.com/articles/s41590-026-02671-8#Aff1),[2](https://www.nature.com/articles/s41590-026-02671-8#Aff2) Show authors [_Nature Immunology_](https://www.nature.com/ni) (2026) [Cite this article](https://www.nature.com/articles/s41590-026-02671-8#citeas) Save article [ View saved research ](https://www.nature.com/saved-research) ## 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. ### Explore related subjects Discover the latest articles and news in related subjects. * [Cancer](https://www.nature.com/subjects/cancer) * [Infectious diseases](https://www.nature.com/subjects/infectious-diseases) * [Inflammation](https://www.nature.com/subjects/inflammation) * [Neutrophils](https://www.nature.com/subjects/neutrophils) * [Neutrophil Phenotypes in Autoimmune and Inflammatory Disease](https://www.nature.com/subjects/neutrophil-phenotypes-in-autoimmune-and-inflammatory-disease) ## Main Neutrophils are key innate immune cells. Beyond their antimicrobial functions, they also modulate adaptive immunity, support tissue repair and homeostasis, and contribute to the pathogenesis of several diseases[1](https://www.nature.com/articles/s41590-026-02671-8#ref-CR1 "Ng, L. G., Ostuni, R. & Hidalgo, A. Heterogeneity of neutrophils. Nat. Rev. Immunol. 19, 255–265 \(2019\)."),[2](https://www.nature.com/articles/s41590-026-02671-8#ref-CR2 "Siwicki, M. & Kubes, P. Neutrophils in host defense, healing, and hypersensitivity: dynamic cells within a dynamic host. J. Allergy Clin. Immunol. 151, 634–655 \(2023\)."). Single-cell RNA sequencing (scRNA-seq) has revealed transcriptional heterogeneity in neutrophils, both at steady state and in disease, including infection and cancer[3](https://www.nature.com/articles/s41590-026-02671-8#ref-CR3 "Montaldo, E. et al. Cellular and transcriptional dynamics of human neutrophils at steady state and upon stress. Nat. Immunol. 23, 1470–1483 \(2022\)."),[4](https://www.nature.com/articles/s41590-026-02671-8#ref-CR4 "Wigerblad, G. et al. Single-cell analysis reveals the range of transcriptional states of circulating human neutrophils. J. Immunol. 209, 772–782 \(2022\)."),[5](https://www.nature.com/articles/s41590-026-02671-8#ref-CR5 "Schulte-Schrepping, J. et al. Severe COVID-19 is marked by a dysregulated myeloid cell compartment. Cell 182, 1419–1440 \(2020\)."),[6](https://www.nature.com/articles/s41590-026-02671-8#ref-CR6 "Kwok, A. J. et al. Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis. Nat. Immunol. 24, 767–779 \(2023\)."),[7](https://www.nature.com/articles/s41590-026-02671-8#ref-CR7 "Wu, Y. et al. Neutrophil profiling illuminates anti-tumor antigen-presenting potency. Cell 187, 1422–1439 \(2024\)."). Neutrophil-driven transcriptomic dysregulation has been associated with risk factors for severe infection even before infection onset[8](https://www.nature.com/articles/s41590-026-02671-8#ref-CR8 "Ganesan, A. et al. A conserved immune dysregulation signature is associated with infection severity, risk factors prior to infection, and treatment response. Immunity 58, 2104–2119 \(2025\)."), and with disease severity and mortality in critical illnesses[9](https://www.nature.com/articles/s41590-026-02671-8#ref-CR9 "Moore, A. R. et al. A consensus immune dysregulation framework for sepsis and critical illnesses. Nat. Med. 31, 4084–4096 \(2025\)."). This evolving knowledge underscores the complexity of neutrophil states in both health and disease. However, current scRNA-seq studies typically focus on only a few conditions and use different sequencing protocols, analytical pipelines and nomenclatures. Therefore, a systematic single-cell analysis across diverse cohorts is needed to unify our understanding of neutrophil subsets and transcriptional states across several conditions, tissues and species. In this study, we described an integrated single-cell atlas of human neutrophils (SCAHN) consisting of 1 million neutrophils from 781 samples and 43 datasets. We identified robust changes in neutrophils related to infection severity, cancer, immune suppression, sex and clinical outcomes. We used SCAHN to define neutrophil-specific transcriptomic signatures and quantify those compartments in 17,023 bulk transcriptomes, and revealed the association of neutrophil signatures with metabolic dysfunction and survival. Using two clinical cohorts consisting of over 430,000 electronic health records (EHRs), we analyzed the association between neutrophils and higher risk of chronic diseases and all-cause mortality. Together, our systematic analysis of the neutrophil transcriptome established a unified understanding of neutrophil heterogeneity and functional diversity across health and disease, enabled cross-species comparison of neutrophils, identified associations with poor health outcomes and provided resources and insights for new diagnostics and therapies targeting neutrophils. ## Results ### Single-cell atlas describes human neutrophil heterogeneity To characterize the neutrophil transcriptomic landscape in health and disease, we searched public repositories for human scRNA-seq datasets with neutrophils profiled. We integrated 1 million human neutrophils from 781 samples (43 datasets) to create SCAHN, encompassing 7 sequencing platforms, 9 countries and over 20 tissues and diseases (Fig. [1a](https://www.nature.com/articles/s41590-026-02671-8#Fig1) and Supplementary Table [1](https://www.nature.com/articles/s41590-026-02671-8#MOESM3)). The most profiled tissues included peripheral blood, cord blood, bone marrow, lung, liver, colorectum, pancreas and spleen (Fig. [1b,c](https://www.nature.com/articles/s41590-026-02671-8#Fig1)). The neutrophils came from healthy individuals or those with infection, lung cancer, cardiovascular disease (CVD), autoimmune diseases or other conditions (Fig. [1b,c](https://www.nature.com/articles/s41590-026-02671-8#Fig1)). The median proportion of neutrophils was 45% in whole blood and 4% in peripheral blood mononuclear cell (PBMC) samples (Fig. [1d](https://www.nature.com/articles/s41590-026-02671-8#Fig1)). In whole blood, the median neutrophil proportion was 27% for 10x Chromium and 72% for BD Rhapsody (Fig. [1d](https://www.nature.com/articles/s41590-026-02671-8#Fig1)). Genes and reads detected per neutrophil did not differ consistently across technical variables such as sequencing platform, sample preservation or sample type (Supplementary Fig. [1a–c](https://www.nature.com/articles/s41590-026-02671-8#MOESM1)). **Fig. 1: SCAHN curates and integrates a comprehensive single-cell atlas of human neutrophils.** ![Fig. 1: SCAHN curates and integrates a comprehensive single-cell atlas of human neutrophils.](https://media.springernature.com/lw685/springer-static/image/art%3A10.1038%2Fs41590-026-02671-8/MediaObjects/41590_2026_2671_Fig1_HTML.png) [Full size image](https://www.nature.com/articles/s41590-026-02671-8/figures/1) **a** , Schematic showing the collection and processing of human scRNA-seq datasets (Supplementary Table [1](https://www.nature.com/articles/s41590-026-02671-8#MOESM3)), and the generation of SCAHN by integrating and clustering neutrophils from each dataset. **b** , Uniform manifold approximation and projections (UMAPs) showing the tissue (top) and condition (bottom) composition of SCAHN neutrophils. Tissues represented in SCAHN are peripheral blood (samples _n_ = 385); cord blood (13); bone marrow (31); lung (100); bronchoalveolar lavage fluid (11); sputum (30); liver (71); colore
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