Rhamnose-mediated modulation of hair follicle growth: insights from chemical genomics

Pursuing compounds capable of stimulating hair follicle growth or regeneration presents a significant challenge in dermatological research. Dermal papilla (DP) cells, which serve as a dynamic niche for hair follicle stem cells, are often used to identify hair growth-promoting agents as a screening model. Here, we integrated human scalp single-cell RNA sequencing data with human DP cells (hDPCs) gene expression profiles to develop a gene panel for assessing hair follicle inductive potential, then applied a high-throughput sequencing-based high-throughput screening (HTS2) method to quantify the gene expressions of hDPCs perturbed by over 2000 small molecules. Notably, rhamnose was identified as a compound that restored the expression of hair-inducing genes in hDPCs. More importantly, the topical application of rhamnose accelerated hair follicle regeneration by promoting hair cycle into the anagen phase. Transcriptome and central carbon metabolism analyses revealed that rhamnose induced glucose metabolism remodeling favoring glycolysis in mice. A similar phenotype was also observed in rhamnose-treated hDPCs, as demonstrated by glycolysis and mitochondrial stress tests. The present study introduces a novel methodology for evaluating hair-inducing agents and provides valuable insights into the cellular and molecular mechanisms underlying the hair growth-promoting effects of rhamnose. These findings highlight the potential for the therapeutic application of rhamnose in the treatment of alopecia.