Androgenetic alopecia (Androgenetic Alopecia) is characterized by progressive miniaturization of hair, forming a distinctive patterned baldness in the scalp; yet, the mechanisms for hair miniaturization in this disease remain largely unknown. Here by single-cell transcriptome analysis, we describe a concise...
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Abstract
Androgenetic alopecia (Androgenetic Alopecia) is characterized by progressive miniaturization of hair, forming a distinctive patterned baldness in the scalp; yet, the mechanisms for hair miniaturization in this disease remain largely unknown. Here by single-cell transcriptome analysis, we describe a concise single-cell atlas, and identify the early changes in cell subpopulations, hair follicle (HF) stem cell fate determination and cell-cell communications in Androgenetic Alopecia anagen HF units. Thereinto, apoptotic loss of HF progenitor cells is significantly increased, correlated with HF miniaturization in Androgenetic Alopecia. Mechanistically, enhanced contraction of connective tissue sheath (CTS) activates the mechanosensitive channel PIEZO1, which triggers ectopic apoptosis of progenitor cells in human anagen HFs. Continuous CTS contraction during Androgenetic Alopecia causes long-term loss of progenitor cells via inducing persistent ectopic apoptosis through PIEZO1, eventually leading to premature hair regression. Most importantly, we show that targeting CTS contraction by ML-7, a selective myosin light chain kinase (MLCK) inhibitor, can obviously improve the growth of HFs from balding scalps of Androgenetic Alopecia patients. Our study reveals the cellular hierarchies and identifies CTS with increased muscle contraction activity as the key determinant of premature hair regression in Androgenetic Alopecia, highlighting CTS surrounding human HF as therapeutic targets for treating this disorder.
pubmed.ncbi.nlm.nih.gov
