Mechanical Tension Mobilizes Lgr6 Epidermal Stem Cells to Drive Skin Growth

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Apr 27

PMID 35476447

Authors

Yingchao Xue

Chenyi Lyu

Ainsley Taylor

Amy van Ee

Ashley Kiemen

Younggeun Choi

Nima Khavanian

Dominic Henn

Chaewon Lee

Lisa Hwang

Eric Wier

Saifeng Wang

Sam Lee

Ang Li

Charles Kirby

Gaofeng Wang

Pei-Hsun Wu

Denis Wirtz

Luis A Garza

Sashank K Reddy

Affiliations

Soon will be listed here.

Abstract

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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