Human hair follicle epithelial stem cells: Implication on hair diseases pathogenesis and therapeutics

Abstract

Hair follicle epithelial stem cells (HFeSCs) in the bulge region are emerging targets for therapeutic intervention or candidate for hair regeneration due to their self-renewal capacity and ability to drive the hair cycle. However, most of the current understanding of HFeSCs is based on mouse models, which may not fully reflect human biology. Therefore, understanding the characteristics and regulatory mechanisms of human HFeSCs is essential for advancing clinical applications. This review summarizes recent advances in identifying human HFeSC markers and the molecular mechanisms that control their activity, including signaling pathways and endocrine hormones. We also explore current knowledge on how HFeSCs are altered in non-scarring alopecia, scarring alopecia, and age-related hair loss. In addition, the therapeutic potential of human HFeSCs in the treatment of hair disorders, as well as the current challenges in achieving de novo hair regeneration and precise in situ modulation of HFeSCs, is discussed. Future single-cell multi-omic studies could help elucidate the biology of HFeSCs in humans, potentially guiding new therapeutic strategies for alopecia.