Hair follicle bulge cells constitute a collection of adult somatic stem cells responsible for the continual renewal of the hair follicle. We originally identified cytokeratin 15 (K15) expression as a marker for these cells and developed several transgenic mouse models using the K15 promoter to further study the bulge cells. We isolated bulge cells and demonstrated that they possessed an epithelial stem cell phenotype of quiescence, high proliferative potential and multipotency. We also characterized the cells at the molecular level using microarrays and identified approximately 150 differentially expressed genes in these cells. Through genetic lineage analysis using an inducible K15-CrePR;R26R bigenic mouse, we showed that bulge cells generate all of the epithelial lineages within the lower anagen hair follicle. Destruction of bulge cells caused loss of the hair follicle.
To assess the role of hair follicle stem cells in human alopecias, we studied bald and non-bald scalp from men with androgenetic alopecia. We assessed presence of hair follicle stem and progenitor cells using flow cytometry to quantitate cells expressing K15, CD200, CD34 and Alpha-6-integrin. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. Cells with the highest level of KRT15 expression were maintained in bald scalp; however, distinct populations of CD200high ITGA6high cells and CD34-positive cells were markedly diminished. The diminished populations localized closely to the stem-cell rich bulge area but were larger and more proliferative than the bulge stem cells. These findings demonstrate the utility of FACS analysis for studying stem and progenitor cells in human alopecias, and suggest that a defect in stem cell activation plays a role in the pathogenesis of androgenetic alopecia.