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Mechanical tension mobilizes Lgr6+ epidermal stem cells to drive skin growth.
Xue, Yingchao; Lyu, Chenyi; Taylor, Ainsley; Van Ee, Amy; Kiemen, Ashley; Choi, YoungGeun; Khavanian, Nima; Henn, Dominic; Lee, Chaewon; Hwang, Lisa; Wier, Eric; Wang, Saifeng; Lee, Sam; Li, Ang; Kirby, Charles; Wang, Gaofeng; Wu, Pei-Hsun; Wirtz, Denis; Garza, Luis A; Reddy, Sashank K.
Affiliation
  • Xue Y; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Lyu C; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Taylor A; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Van Ee A; Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Kiemen A; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Choi Y; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Khavanian N; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Henn D; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Lee C; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Hwang L; Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Wier E; Department of Plastic Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • Wang S; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Lee S; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Li A; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Kirby C; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Wang G; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Wu PH; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Wirtz D; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Garza LA; Department of Dermatology, Johns Hopkins University, Baltimore, MD 21231, USA.
  • Reddy SK; Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Sci Adv ; 8(17): eabl8698, 2022 04 29.
Article in En | MEDLINE | ID: mdl-35476447
Uniquely among mammalian organs, skin is capable of marked size change in adults, yet the mechanisms underlying this notable capacity are unclear. Here, we use a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin. We find that most growth is driven by the proliferation of the epidermis in response to mechanical tension, with more limited changes in dermal and subdermal compartments. Epidermal growth is achieved through preferential activation and differentiation of Lgr6+ stem cells of the epidermis, driven in part by the Hippo pathway. By single-cell RNA sequencing, we uncover further changes in mechanosensitive and metabolic pathways underlying growth control in the skin. These studies point to therapeutic strategies to enhance skin growth and establish a platform for understanding organ size dynamics in adult mammals.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin / Stem Cells / Receptors, G-Protein-Coupled / Epidermal Cells Limits: Animals Language: En Journal: Sci Adv Year: 2022 Document type: Article Affiliation country: United States Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Skin / Stem Cells / Receptors, G-Protein-Coupled / Epidermal Cells Limits: Animals Language: En Journal: Sci Adv Year: 2022 Document type: Article Affiliation country: United States Country of publication: United States