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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1306353
Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in an mice expanded skin model
Provisionally accepted- 1 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2 Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, Shanghai Municipality, China
- 3 Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China
Background: Mechanical stretch-mediated tissue expansion is effective for obtaining extra skin and soft tissue required for the repair of defects or reconstruction of surface organs. Understanding the cellular and molecular mechanisms and identifying hub genes and key cell types associated with skin expansion could help predict the success of skin growth during expansion procedures. Methods: We analyzed murine chip sequencing data and single-cell sequencing data available from the Gene Expression Omnibus database. Based on the differentially expressed and epithelial–mesenchymal transition-related genes, random forest and protein-protein interaction network analysis identified hub genes for predicting skin regeneration in tissue expansion. The fate of the cell subpopulations, expression of hub genes in different cell types, and their communication were also assessed. Results: Five genes, integrin beta 5 (Itgb5), tropomyosin 1 (Tpm1), secreted frizzled-related protein-1 (Sfrp1), Notch1, and insulin-like growth factor binding protein 2 (Igfbp2), were identified as having the greatest impact on prediction accuracy. These hub genes were primarily enriched in the Notch and phosphoinositide 3-kinase-AKT pathways. Immune cell infiltration analysis further revealed that mast cell infiltration was significantly higher in the expanded skin group than that in the control group. According to single-cell data, the interactions between epithelial cells, stem cells, and other cell types were higher in the expanded skin group than those in the control group. Moreover, Tpm1, Sfrp1, and Notch1 were highly expressed in all epithelial and stem cell subgroups. Conclusions: The hub genes, Notch1, Tpm1 and Sfrp1, and their associated signaling pathways such as Notch and Wnt signaling and functions in key cell subsets highlight prospective therapeutic strategies to enhance skin growth under mechanical expansion. Moreover, mast cell activation and infiltration may trigger immune responses in the expanded skin, which requires further investigation.
Keywords: Skin Regeneration, Tissue Expansion, Hub genes, microenvironment, Mast cell (MC)
Received: 01 Nov 2023; Accepted: 06 Nov 2024.
Copyright: © 2024 Wang, Qi, Yu, Zhou, Wang, Liu, Jin, Luo, Ma, Lu and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yinmin Wang, Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200011, China
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