Hair follicles repeatedly regress and reconstitute themselves, suggesting the presence of intrinsic tissue stem cells. Using label-retaining cell technique to detect slow-cycling stem cells, hair follicle stem cells were detected in the bulge region of the outer root sheath, which provides the insertion point for the arrector pili muscle and marks the bottom of the permanent portion of hair follicles. Later studies elucidated important stem cell characteristics of the bulge cells, including high proliferative capacity and multipotency to regenerate the pilosebaceous unit as well as epidermis. Isolation of living bulge cells is now feasible. In addition, microarray analyses revealed the global gene expression profile of the bulge cells. However, most of those studies were performed in mouse hair follicles and our understanding of human bulge cells has been limited. Recently, remarkable progress was made in human bulge cell biology. The morphologically ill-defined human bulge boundary was precisely determined by the distribution of label-retaining cells. Laser capture microdissection enabled accurate isolation of human bulge cells and control cell populations. Microarray comparison analyses between isolated bulge and nonbulge cells elucidated the molecular signature of human bulge cells and identified cell surface markers for living bulge cell isolation. Importantly, isolated living human bulge cells demonstrated stem cell characteristics in vitro. In this review, recent advances in hair follicle bulge cell research are summarized, especially focusing on the characterization and isolation of human bulge cells.
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