Distinct diversity of skin cell populations of rhinophyma and 1 hypertrophic scar illustrated by scRNA-seq 2

Qiannan Li^1,2Lanxin Geng²Xufeng He²Xiang-yu Wei²Cheng Zhang²Hui-Min Zhang²Xiang He^2*Yiyang Hu^2*Wuqing Wang^2*

• ¹Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ²Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China

Abstract 31 Introduction: The clinical manifestations and presentation of rhinophyma closely 32 resemble those of hypertrophic scar tissue, both presenting as firm, fibrotic growths. 33 Despite this phenotypic similarity, a critical divergence is observed following surgical 34 intervention: the affected skin in rhinophyma can revert to its normal state without scar 35 recurrence, a favorable outcome starkly contrasting with the behavior of hypertrophic 36 scars. The underlying mechanisms for this phenomenon have yet to be elucidated. The 37 aim of this study is to uncover the cellular and molecular disparities between these two 38 pathological conditions using single-cell sequencing technology to resolve this clinical 39 paradox. The objective of this study is to compare the single-cell transcriptomic profiles 40 of rhinophyma and hypertrophic scar tissues to identify key cell types and molecular 41 pathways that may account for the distinct healing fate of rhinophyma post-surgery and 42 provide novel insights for the prevention and treatment of hypertrophic scars. 43 Methods and Results: We isolated single cells from rhinophyma and hypertrophic scar 44 tissues and conducted transcriptomic analysis using high-throughput single-cell RNA 45 sequencing technology. Employing bioinformatics methods, we analyzed the data to 46 identify differentially expressed genes and cellular subpopulations. Our results indicate 47 that epithelial cells in hypertrophic scar tissues exhibit distinct fibrotic characteristics 48 not observed in rhinophyma tissues. Vascular structures in hypertrophic scar tissues are 49 enveloped by a significant number of stromal cells, in contrast to the leaky vascular 50 profiles observed in rhinophyma tissues. Furthermore, keratinocytes in hypertrophic 51 scars display disordered proliferation, while the number of immune cells in rhinophyma 52 is significantly higher than in hypertrophic scar tissues. 53 Conclusion: These findings reveal fundamental differences in cellular composition and 54 functionality between rhinophyma and hypertrophic scar tissues, the intrinsic 55 differences in the tissue microenvironment predispose them to divergent healing 56 trajectories following the same insult, offering new perspectives on the healing process 57 of rhinophyma post-surgery and potentially providing molecular targets for the 58 development of scar prevention strategies.