Single-cell transcriptomics reveals lineage trajectory of human scalp hair follicle and informs mechanisms of hair graying
Authors
Sijie Wu, Yao Yu, Caiyue Liu, Xia Zhang, Peiying Zhu, You Peng, Xinyu Yan, Yin Li, Peng Hua, Qingfeng Li, Sijia Wang & Liang Zhang
Institution
University of Chinese Academy of Sciences, CAS, Shanghai
Country
China
Year
2022
Journal
Cell Discovery
Abstract
Hair conditions, such as hair loss and graying, are prevalent human conditions. But they are often poorly controlled due to our insufficient understanding of human scalp hair follicle (hsHF) in health and disease. Here we describe a comprehensive single-cell RNA-seq (scRNA-seq) analysis on highly purified black and early-stage graying hsHFs. Based on these, a concise single-cell atlas for hsHF and its early graying changes is generated and verified using samples from multiple independent individuals. These data reveal the lineage trajectory of hsHF in unprecedented detail and uncover its multiple unexpected features not found in mouse HFs, including the presence of an innerbulge like compartment in the growing phase, lack of a discrete companion layer, and enrichment of EMT features in HF stem cells (HFSCs). Moreover, we demonstrate that besides melanocyte depletion, early-stage human hair graying is also associated with specific depletion of matrix hair progenitors but not HFSCs. The hair progenitors' depletion is accompanied by their P53 pathway activation whose pharmaceutical blockade can ameliorate hair graying in mice, enlightening a promising therapeutic avenue for this prevalent hair condition.