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Spatially resolved proteomic map shows that extracellular matrix regulates epidermal growth

Jun Li (), Jie Ma, Qiyu Zhang, Huizi Gong, Dunqin Gao, Yujie Wang, Biyou Li, Xiao Li, Heyi Zheng, Zhihong Wu, Yunping Zhu () and Ling Leng ()
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Jun Li: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Jie Ma: Beijing Institute of Lifeomics
Qiyu Zhang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Huizi Gong: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Dunqin Gao: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yujie Wang: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Biyou Li: Beijing Institute of Lifeomics
Xiao Li: Beijing Institute of Lifeomics
Heyi Zheng: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Zhihong Wu: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Yunping Zhu: Beijing Institute of Lifeomics
Ling Leng: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Human skin comprises stratified squamous epithelium and dermis with various stromal cells and the extracellular matrix (ECM). The basement membrane (BM), a thin layer at the top of the dermis, serves as a unique niche for determining the fate of epidermal stem cells (EpSCs) by transmitting physical and biochemical signals to establish epidermal cell polarity and maintain the hierarchical structure and function of skin tissue. However, how stem cell niches maintain tissue homeostasis and control wound healing by regulating the behavior of EpSCs is still not completely understood. In this study, a hierarchical skin proteome map is constructed using spatial quantitative proteomics combined with decellularization, laser capture microdissection, and mass spectrometry. The specific functions of different structures of normal native skin tissues or tissues with a dermatologic disease are analyzed in situ. Transforming growth factor-beta (TGFβ)-induced protein ig-h3 (TGFBI), an ECM glycoprotein, in the BM is identified that could enhance the growth and function of EpSCs and promote wound healing. Our results provide insights into the way in which ECM proteins facilitate the growth and function of EpSCs as part of an important niche. The results may benefit the clinical treatment of skin ulcers or diseases with refractory lesions that involve epidermal cell dysfunction and re-epithelialization block in the future.

Date: 2022
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DOI: 10.1038/s41467-022-31659-9

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