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A mathematical framework for human neutrophil state transitions inferred from single-cell RNA sequence data.
Gustaf Wigerblad1, Jonathan Carruthers2, Sumanta Ray3,4
1Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS/National Institutes of Health (NIH)), Bethesda, MD, United States.
Frontiers in Immunology
|November 10, 2025
Summary
Researchers modeled human neutrophil maturation dynamics, identifying distinct states and transition rates. A significant fraction of neutrophils enter an interferon-responsive state, highlighting immune system complexity.
Area of Science:
- Immunology
- Computational Biology
- Systems Biology
Background:
- Neutrophils are key innate immune cells, but their population dynamics and heterogeneity are not fully understood.
- Modeling neutrophil subset dynamics is crucial for understanding immune responses and disease states.
Purpose of the Study:
- To develop a mathematical model describing human neutrophil maturation states and transitions.
- To analyze single-cell gene expression data to define neutrophil subsets and their differentiation pathways.
Main Methods:
- Utilized single-cell gene expression data from healthy human neutrophils.
- Applied pseudo-time analysis to infer differentiation trajectories.
- Developed a mathematical model to capture state transitions and their rates.
- Employed Bayesian inference to model inter-individual variations.
Main Results:
- Identified five distinct neutrophil clusters representing different maturation states.
- Characterized rapid transition from precursor to immature neutrophils (<1 hour).
- Revealed two distinct maturation pathways: a standard pathway and an interferon-responsive pathway (approx. 25% of cells).
- Subsequent transitions along both pathways are slower (mean times >12 hours).
Conclusions:
- The developed model provides a quantitative framework for human neutrophil maturation.
- Neutrophil differentiation involves distinct states and branching pathways, including a significant interferon-responsive subset.
- Understanding these dynamics is essential for comprehending innate immunity and neutrophil heterogeneity.
