Crosstalk between endothelial cells and dermal papilla entails hair regeneration and angiogenesis during aging

作者：Siyi Zhou, Zeming Li, Xinzhu Li, Yuanli Ye, Mengyue Wang, Jingwei Jiang, Lihe Tao, Yan Wang, C.C. Tung, Yongji Chung ., Eun‐Mi Kim, Xinyu Shen, Xuegang Xu, Xiao Xiang, Qiaoli Xie, Jinwei Zhang, Wang Wu, Xia Lin, Cheng‐Ming Chuong, Mingxing Lei · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.05.006 · 被引用次数：35 · 研究领域：Hair Growth and Disorders、Dyeing and Modifying Textile Fibers、Skin Protection and Aging

INTRODUCTION: Tissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vessels respectively, or their interactions. OBJECTIVE: To explore how hair follicles and blood vessels interact to regulate angiogenesis and hair regeneration during aging. METHODS: Single-cell RNA-sequencing (scRNA-seq) analyses were used to identify the declined ability of dermal papilla (DP) and endothelial cells (ECs) during aging. CellChat and CellCall were performed to investigate interaction between DP and ECs. Single-cell metabolism (scMetabolism) analysis and iPATH were applied to analyze downstream metabolites in DP and ECs. Hair-plucking model and mouse cell organoid model were used for functional studies. RESULTS: During aging, distance and interaction between DP and ECs are decreased. DP interacts with ECs, with decreased EDN1-EDNRA signaling from ECs to DP and CTF1-IL6ST signaling from DP to ECs during aging. ECs-secreted EDN1 binds to DP-expressed EDNRA which enhances Taurine (TA) metabolism to promote hair regeneration. DP-emitted CTF1 binds to ECs-expressed IL6ST which activates alpha-linolenic acid (ALA) metabolism to promote angiogenesis. Activated EDN1-EDNRA-TA signaling promotes hair regeneration in aged mouse skin and in organoid cultures, and increased CTF1-IL6ST-ALA s...