Fig. 1. Hair follicle SC populations and their supposed location during the hair cycle. Cyclical changes in hair follicle growth are divided into different stages, referred to as anagen, catagen, and telogen. Hair follicle epithelial and melanocyte SCs localize to the bulge at the site of arrector pili muscle insertion (see blow-up). During anagen, rapidly proliferating progenitor cells in the bulb generate the hair shaft and its surrounding inner root sheath. The onset of catagen is marked by completion of proliferation as well as by apoptosis of the epithelial cells below the bulge. The mesenchymally-derived dermal papilla survives catagen and moves to the lowermost portion of the bulge during telogen, which then forms the secondary hair germ at its base as a pool for melanocyte SCs, which are moved down from the bulge, and maybe for a second epithelial SC population (see blow-up). As the new hair shaft grows in, the old hair is shed. Possible SCs populations and their locations in the human hair follicle are indicated in the anagen VI hair follicle blow-up illustrations.

Fig. 2. Cellular metabolism and SC function. Elements of the local environment that participate in regulating the system of SCs are depicted. SC function include the architectural niche, physical engagement of the cell membrane with molecules on neighboring cells, signaling interactions of SC and niche or descendent cells, endocrine and paracrine signals, neural signals and metabolic products.

Fig. 3. Simplified hierarchy and interactions of eSC regulators. Red color denotes a relative “stem-ness”, green color indicates increasing commitment towards a hair follicle-type epithelial differentiation pathway. Abbreviations in common use: Lhx2, LIM homeobox protein 2 (NM_010710); p63, tumor protein p73-like (TP73L, NM_003722); NFκB, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon (NFKBIE, NM_518507); Wnt, wingless-type MMTV integration site family (WNT, NM_003393); Tcf3, transcription factor 3 (Tcfe2a, NM_011548); Noggin, bone morphogenetic protein 4 (NOG, NM_130851); Bmp, bone morphogenetic protein 1 (BMP1, NM_006129); Rac1, ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1, AJ132695); Shh, sonic hedgehog homolog (SHH, NM_000193). Modified after Tiede and Paus (2006).

Fig. 4. Expression of K15 in the bulge region (A) and in the lower portion (B) of human anagen VI hair follicle. Human scalp sections were stained against keratin 15 (LHK15-antibody, Chemicon, USA) and visualized by immunofluorescence (A) and immunohistochemistry (B).

A pragmatic approach to identifying and distinguishing distinct hair follicle stem cell populations and their progeny

Abbreviations: SC, stem cells; HF, hair follicle; ORS, outer root sheath; ES, embryonic stem cells; TA, transient amplifying cells.

+++most usable positive marker.

−−−most usable negative marker.