Disrupted Cholesterol Biosynthesis and Hair Follicle Stem Cell Impairment in the Onset of Alopecia

November 2023 in “ bioRxiv (Cold Spring Harbor Laboratory) ”

Leemon Nikhila, Surya Suresh, Shahul Hameed Najeeb, Thankachan Mangalathettu Binumon, Aayush Gupta, Sandeep Gopalakrishnan, Parameswara Panicker Sreejith

Studysummary This study found that disrupted cholesterol homeostasis impairs hair regrowth in individuals with primary cicatricial alopecia by damaging hair follicle stem cells, highlighting the importance of cholesterol in maintaining stem cell function and hair follicle integrity. Our plain-language summary of this paper — not a Tressless recommendation.

The study investigates the role of disrupted cholesterol homeostasis in hair follicle stem cells (HFSCs) and its impact on hair follicle cycling, particularly in primary cicatricial alopecia (PCA). It was found that patients with PCA exhibit decreased expression of HFSC marker genes, and experiments with 7-dehydrocholesterol (7DHC) and BM15766 in human cells, mice, and organoid cultures showed that cholesterol inhibition and sterol intermediate accumulation disrupt stem cell characteristics and prevent hair regrowth. This leads to apoptosis in stem cells, highlighting the critical role of cholesterol production in maintaining HFSC integrity and functionality. The findings provide new insights into the progression of alopecia and the involvement of sterol intermediates in hair follicle cycling and stem cell function.

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research Hairy Tale of Signaling in Hair Follicle Development and Cycling

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