Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

TLDR

Androgenetic alopecia is marked by a pronounced reduction in hair follicle size, potentially due to loss of follicular stem or progenitor cells. The study aimed to determine whether bald and non‑bald scalp from AGA patients differ in the presence of hair follicle stem and progenitor cells. Flow cytometry quantified cells expressing cytokeratin‑15, CD200, CD34, and integrin‑α6. KRT15^hi stem cells persist in bald scalp, but CD200^hiITGA6^hi and CD34^hi progenitor populations are markedly reduced, and functional assays confirm these progenitors are multipotent, indicating a defect in stem‑to‑progenitor conversion contributes to AGA.

Abstract

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15hi stem cells were maintained in bald scalp samples. However, CD200hiITGA6hi and CD34hi cell populations — which both possessed a progenitor phenotype, in that they localized closely to the stem cell–rich bulge area but were larger and more proliferative than the KRT15hi stem cells — were markedly diminished. In functional assays, analogous CD200hiItga6hi cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.