Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model

BackgroundMechanical 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 e...

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Main Authors: Yinmin Wang, Wenxiao Qi, Shun Yu, Xianyu Zhou, Xiuxia Wang, Fei Liu, Rui Jin, Xusong Luo, Qiangliang Ma, Lin Lu, Jun Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1306353/full
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author Yinmin Wang
Wenxiao Qi
Shun Yu
Xianyu Zhou
Xiuxia Wang
Fei Liu
Fei Liu
Rui Jin
Xusong Luo
Qiangliang Ma
Lin Lu
Jun Yang
author_facet Yinmin Wang
Wenxiao Qi
Shun Yu
Xianyu Zhou
Xiuxia Wang
Fei Liu
Fei Liu
Rui Jin
Xusong Luo
Qiangliang Ma
Lin Lu
Jun Yang
author_sort Yinmin Wang
collection DOAJ
description BackgroundMechanical 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.MethodsWe 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.ResultsFive 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.ConclusionsThe 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.
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spelling doaj-art-5ce2e9603e5f4978a42c05075b44f8a72025-08-20T02:30:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.13063531306353Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin modelYinmin Wang0Wenxiao Qi1Shun Yu2Xianyu Zhou3Xiuxia Wang4Fei Liu5Fei Liu6Rui Jin7Xusong Luo8Qiangliang Ma9Lin Lu10Jun Yang11Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Sports Medicine, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaAffiliated Hospital of Jiangnan University, Wuxi, Jiangsu, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaThe First People’s Hospital of the Lancang Lahu Autonomous County, Puer, Yunnan, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Dermatology, Traditional Chinese Medicine Hospital, Ili Kazakh Autonomous State, Yining, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, ChinaBackgroundMechanical 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.MethodsWe 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.ResultsFive 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.ConclusionsThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1306353/fullskin regenerationtissue expansionhub genesmicroenvironmentmast cell (MC)
spellingShingle Yinmin Wang
Wenxiao Qi
Shun Yu
Xianyu Zhou
Xiuxia Wang
Fei Liu
Fei Liu
Rui Jin
Xusong Luo
Qiangliang Ma
Lin Lu
Jun Yang
Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model
Frontiers in Immunology
skin regeneration
tissue expansion
hub genes
microenvironment
mast cell (MC)
title Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model
title_full Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model
title_fullStr Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model
title_full_unstemmed Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model
title_short Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model
title_sort comprehensive analysis of skin growth related hub genes and microenvironment characterization in a mouse expanded skin model
topic skin regeneration
tissue expansion
hub genes
microenvironment
mast cell (MC)
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1306353/full
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