Dominant role of the niche in melanocyte stem-cell fate determination

Abstract

Stem cells which have the capacity to self-renew and generate differentiated progeny are thought to be maintained in a specific environment known as a niche. The localization of the niche, however, remains largely obscure for most stem-cell systems. Melanocytes (pigment cells) in hair follicles proliferate and differentiate closely coupled to the hair regeneration cycle. Here we report that stem cells of the melanocyte lineage can be identified, using Dct-lacZ transgenic mice, in the lower permanent portion of mouse hair follicles throughout the hair cycle. It is only the population in this region that fulfils the criteria for stem cells, being immature, slow cycling, self-maintaining and fully competent in regenerating progeny on activation at early anagen (the growing phase of hair follicles). Induction of the re-pigmentation process in K14-steel factor transgenic mice demonstrates that a portion of amplifying stem-cell progeny can migrate out from the niche and retain sufficient self-renewing capability to function as stem cells after repopulation into vacant niches. Our data indicate that the niche has a dominant role in the fate determination of melanocyte stem-cell progeny.

Biology of Human Hair: Know Your Hair to Control It

“…In addition, HF also contained multiple target structures for innovative therapeutic approaches. These include specific cell populations in and around the HF, such as immune cells, stem cells and melanocytes, sebaceous glands and perifollicular blood vessels [154][155][156].…”

The proliferating field of neural crest stem cells

“…The cyclical turnover of hair during the moult cycle is accompanied by a similar turnover of melanocytes; hence, a stem cell source of melanocyte renewal was anticipated. Candidate melanocyte stem cells (MSCs) were first identified in the lower permanent portion or bulge of the hair follicle as Dct-LacZ ϩ cells resistant to treatment with ACK2, a monoclonal c-Kit blocking antibody (Nishimura et al, 2002). In the resting phase (telogen), MSCs are quiescent, but their division is activated during the growth phase of the hair follicle (anagen) to supply proliferating and differentiating progeny to pigment the maturing hair.…”

“…In the resting phase (telogen), MSCs are quiescent, but their division is activated during the growth phase of the hair follicle (anagen) to supply proliferating and differentiating progeny to pigment the maturing hair. These cells colonized the bulge of early hair follicles by postnatal day 0.5, were shown to be slow cycling, and lacked melanin granules (Nishimura et al, 2002). Unlike other neural crest-derived stem cells, the potency of MSCs has not been examined; although they generate melanocytes in vivo, it remains to be seen whether they could generate other cell types in culture.…”

“…Unlike other neural crest-derived stem cells, the potency of MSCs has not been examined; although they generate melanocytes in vivo, it remains to be seen whether they could generate other cell types in culture. Evidence supporting the self-renewal of MSCs in the hair follicle throughout the lifetime of the mouse has been presented (Nishimura et al, 2002), but this finding needs to be tested directly in culture with purified MSCs.…”

“…The ability to identify MSCs in their niche has allowed some characterization of their expression profile in vivo (Nishimura et al, 2002;Lang et al, 2005;Osawa et al, 2005). Using both immunofluorescent staining of sectioned mouse skin and single-cell expression profiling of microdissected, genetically labeled MSCs, a molecular…”