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Updated: Aug 9, 2025
Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Transcriptional heterogeneity in human diabetic foot wounds
Abstract:
Wound repair requires the coordination of multiple cell types including immune cells and tissue resident cells to coordinate healing and return of tissue function. Diabetic foot ulceration is a type of chronic wound that impacts over 4 million patients in the US and over 7 million worldwide (Edmonds et al., 2021). Yet, the cellular and molecular mechanisms that go awry in these wounds are not fully understood. Here, by profiling chronic foot ulcers from non-diabetic (NDFUs) and diabetic (DFUs) patients using single-cell RNA sequencing, we find that DFUs display transcription changes that implicate reduced keratinocyte differentiation, altered fibroblast function and lineages, and defects in macrophage metabolism, inflammation, and ECM production compared to NDFUs. Furthermore, analysis of cellular interactions reveals major alterations in several signaling pathways that are altered in DFUs. These data provide a view of the mechanisms by which diabetes alters healing of foot ulcers and may provide therapeutic avenues for DFU treatments.
Insights
Diabetic foot ulcers show impaired healing due to cellular defects. This study reveals molecular changes in skin cells and immune cells in diabetic foot ulcers (DFUs), offering potential new treatments.
Area of Science:
- Cellular and Molecular Mechanisms of Wound Healing
- Diabetic Complications and Tissue Repair
Background:
- Diabetic foot ulcers (DFUs) are a significant global health burden, affecting millions with chronic wounds.
- The precise cellular and molecular underpinnings of impaired DFU healing remain incompletely understood.
Approach:
- Single-cell RNA sequencing was employed to profile chronic foot ulcers from both non-diabetic (NDFU) and diabetic (DFU) patients.
- Comparative analysis identified distinct transcriptional profiles and cellular interaction alterations in DFUs versus NDFUs.
Key Points:
- DFUs exhibit reduced keratinocyte differentiation and altered fibroblast function and lineages.
- Macrophage dysfunction in DFUs includes defects in metabolism, inflammation, and extracellular matrix (ECM) production.
- Significant alterations in key signaling pathways were observed in DFUs compared to NDFUs.
Conclusions:
- Diabetes profoundly impacts foot ulcer healing at the cellular and molecular level.
- Understanding these DFU-specific mechanisms provides a foundation for developing targeted therapeutic strategies.
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