ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1654015
This article is part of the Research TopicMathematical Modeling in Discovery and Analysis of Immune ResponsesView all 12 articles
A mathematical framework for human neutrophil state transitions inferred from single-cell RNA sequence data
Provisionally accepted
Gustaf Wigerblad1
Jonathan Carruthers2
Sumanta Ray3
Thomas Finnie2
Grant Lythe4
Saumyadipta Pyne5*
Carmen Molina-París6*
Mariana Julieta Kaplan1*- 1National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, United States
- 2UK Health Security Agency Porton, Salisbury, United Kingdom
- 3The West Bengal National University of Juridical Sciences, Kolkata, India
- 4University of Leeds, Leeds, United Kingdom
- 5University of California Santa Barbara, Santa Barbara, United States
- 6Theoretical Division, Los Alamos National Laboratory (DOE), Los Alamos, United States
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Neutrophils, the most abundant immune cells in the human circulation, play a central role in the innate immune system. While neutrophil heterogeneity is a topic of increasing research interest, few efforts have been made to model the dynamics of neutrophil population subsets. We develop a mathematical model to describe the dynamics that characterizes the states and transitions involved in the maturation of human neutrophils. We use single-cell gene expression data to identify five clusters of healthy human neutrophils, and pseudo-time analysis to inform model structure. We find that precursor neutrophils transition into immature neutrophils, which then either transition to an interferon-responsive state or continue to mature through two further states. The key model parameters are the transition rates (the inverse of a transition rate is the mean waiting time in one state before transitioning to another). In this framework, the transition from the precursor to immature state (mean time less than an hour) is more rapid than subsequent transitions (mean times more than 12 hours). Approximately a quarter of neutrophils are estimated to follow the interferon-responsive path; the remainder continue along the standard maturation pathway. We use Bayesian inference to describe the variation, between individuals, in the fraction of cells within each cluster.
Keywords: Neutrophils, states, Transitions, mathematical model, single-cell RNA sequence data
Received: 25 Jun 2025; Accepted: 29 Sep 2025.
Copyright: © 2025 Wigerblad, Carruthers, Ray, Finnie, Lythe, Pyne, Molina-París and Kaplan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Saumyadipta Pyne, spyne@ucsb.edu
Carmen Molina-París, carmen@maths.leeds.ac.uk
Mariana Julieta Kaplan, mariana.kaplan@nih.gov
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