Fibroblast Heterogeneity in Wound Healing Dynamics

Wound healing is orchestrated by a diverse array of fibroblast subtypes that differ in origin, gene expression and functional capacity. Following injury, distinct fibroblast populations emerge in a spatiotemporal sequence to regulate inflammation, extracellular matrix deposition, contraction and remodelling. Some fibroblasts derive from local dermal compartments, while others arise from fascia progenitors or infiltrating myeloid cells, adopting either pro­inflammatory or contractile myofibroblast states. The balance among these subpopulations determines healing outcomes: efficient tissue repair with minimal scarring, chronic non-healing wounds or excessive fibrosis. Advances in single-cell transcriptomics, genetic lineage tracing and spatial profiling have revealed at least a dozen transcriptionally and functionally discrete fibroblast clusters. These clusters exhibit specific signalling sensitivities to retinoic acid, hypoxia and Wnt pathways, reflecting their roles in scar formation, hair follicle regeneration and adipocyte de novo formation. Understanding fibroblast heterogeneity provides avenues for targeted modulation of wound healing dynamics and the design of precision therapies to enhance regeneration, limit fibrosis and restore tissue function.

Research from Nature Portfolio

Recent studies have identified a multipotent fibroblast progenitor marked by CD201 in the fascia, which sequentially gives rise to proinflammatory fibroblasts and myofibroblasts under the control of retinoic acid and hypoxia signalling. Genetic deletion and cell-ablation models demonstrate that tuning CD201+ progenitor differentiation directly affects the timing and quality of wound closure. Complementing this, single-cell transcriptomic analysis in murine skin wounds has delineated a dozen fibroblast clusters, some of which trace back to hematopoietic lineage cells that contribute to adipocyte regeneration. Pseudotime and RNA-velocity analyses reveal both linear differentiation trajectories toward contractile states and parallel lineage branches, underscoring the plasticity of wound fibroblasts and their dual origins in mesenchymal and myeloid compartments.

Fibroblast Heterogeneity in Wound Healing Dynamics publication trend

The graph below shows the total number of articles in fibroblast heterogeneity in wound healing dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Fibroblast: A mesenchymal cell that synthesises extracellular matrix and modulates tissue remodelling.

Myofibroblast: An activated fibroblast characterised by contractile machinery and α-smooth muscle actin expression.

Single-cell RNA sequencing: A method to profile gene expression at the resolution of individual cells.

Extracellular matrix: The network of proteins and polysaccharides that provides structural scaffold and biochemical cues in tissues.

Lineage tracing: Experimental approaches that label specific cell populations to follow their progeny over time.

Paracrine signalling: Local cell–cell communication mediated by secreted factors acting on neighbouring cells.

References

1. CD201+ fascia progenitors choreograph injury repair. Nature (2023).
2. Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds. Nature Communications (2019).
3. A tissue injury sensing and repair pathway distinct from host pathogen defense. Cell (2023).
4. Understanding the impact of fibroblast heterogeneity on skin fibrosis. Disease Models & Mechanisms (2020).
5. Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations. Journal of Investigative Dermatology (2018).