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Single cell transcriptomics reveals the cellular heterogeneity of keloids and the mechanism of their aggressiveness
Xinwei Cheng1, Zhen Gao1, Shengzhou Shan1
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Keloid is a dermatofibrotic disease known for its aggressive nature and characterized by pathological scarring, which often leads to disfigurement and frequent recurrences. Effective therapies for keloids are still limited, presumably due to the inadequate comprehension of their aggressive mechanisms. In our study, we examined the unique scenario where both keloid and non-aggressive pathological scar originate from the same patient, providing a rare opportunity to explore the aggressive mechanisms of keloids through single-cell RNA sequencing. We found that the dominant fibroblast subgroup in keloids is mechanoresponsive group, which showed enhanced mechanotransduction and migration. This mechanoresponsive fibroblast subgroup is likely to be the key cell population and confer aggressive growth of keloids. The results also indicate that the endothelial cells and keratinocytes in keloid involve in endothelial-mesenchymal and epithelial-mesenchymal transitions. This study demonstrated the mechanoresponsive fibroblasts and multiple cellular mesenchymal processes could pave the way for further investigations into the keloid aggressiveness.
Insights
Keloid scars exhibit aggressive growth driven by mechanoresponsive fibroblasts. Understanding these cellular mechanisms offers new therapeutic avenues for pathological scarring.
Area of Science:
- Dermatology
- Cell Biology
- Molecular Biology
Background:
- Keloids are aggressive pathological scars causing disfigurement and recurrence.
- Current keloid therapies are limited by incomplete understanding of disease mechanisms.
Purpose of the Study:
- To investigate the cellular mechanisms underlying keloid aggressiveness.
- To identify key cell populations driving keloid formation using single-cell RNA sequencing.
Main Methods:
- Single-cell RNA sequencing was performed on keloid and non-aggressive scar tissue from the same patient.
- Analysis focused on fibroblast, endothelial cell, and keratinocyte populations.
Main Results:
- A dominant subgroup of mechanoresponsive fibroblasts was identified in keloids, exhibiting enhanced mechanotransduction and migration.
- Endothelial cells and keratinocytes in keloids showed evidence of endothelial-mesenchymal and epithelial-mesenchymal transitions.
Conclusions:
- Mechanoresponsive fibroblasts are likely key drivers of keloid aggressiveness.
- Cellular mesenchymal transitions in multiple cell types contribute to keloid pathology.
- These findings provide a foundation for future research into keloid treatment strategies.
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