Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells
Luis A. Garza, Chao-Chun Yang, Tailun Zhao, Hanz B. Blatt, Michelle Lee, Helen He, David C. Stanton, Lee Carrasco, Jeffrey H. Spiegel, John W. Tobias, George Cotsarelis
Luis A. Garza, Chao-Chun Yang, Tailun Zhao, Hanz B. Blatt, Michelle Lee, Helen He, David C. Stanton, Lee Carrasco, Jeffrey H. Spiegel, John W. Tobias, George Cotsarelis
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Research Article Dermatology

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

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.

Authors

Luis A. Garza, Chao-Chun Yang, Tailun Zhao, Hanz B. Blatt, Michelle Lee, Helen He, David C. Stanton, Lee Carrasco, Jeffrey H. Spiegel, John W. Tobias, George Cotsarelis

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Figure 5

Mouse CD200hiItga6hi cell location, cell cycle status, and gene expression are similar to those of human CD200hiITGA6hi cells.

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Mouse CD200hiItga6hi cell location, cell cycle status, and gene expressi...
(A and B) As assessed by immunohistology of mouse skin, CD200 was expressed in bulge and secondary hair germ cells (A), whereas CD34 was expressed in bulge cells, but not secondary hair germ cells (B). (C) FACS identified a CD200hiItga6hi population. (D) CD200 versus CD34 identified bulge cells (CD200hiCD34+) and secondary hair germ cells (CD200hiCD34–). (E) CD34hiItga6hi cells (Supplemental Figure 6E) overlaying CD200hiItga6hi cells (as in C) demonstrated that CD200hiItga6hi cells extended to a CD34– population, but CD34hiItga6hi cells were entirely CD200+. In F, only the CD200hiItga6hi population is shown, exhibiting overlap to the secondary hair germ. (G) Cell cycle analysis demonstrated the lowest frequency of G0/G1 in CD200hiItga6hi cells in the secondary hair germ (CD34–; n = 3, P = 0.02). (H) Enriched gene lists from microarray expression analysis of human CD200hiITGA6hi, mouse bulge (CD200hiCD34+), and mouse secondary hair germ (CD200hiCD34–) cells demonstrated that the human CD200hiITGA6hi population overlapped with both mouse populations, but more so with murine bulge than with murine secondary hair germ. Scale bars: 100 μm. Numbers within dot plots indicate percent cells in the respective gate or quadrant.