Quiescence is an important feature distinguishing stem cells (SCs) from other compartments for most SC systems. Evidence suggests that the quiescent state is directed by external cues expressed in the presumptive microenvironment, the niche, although the cellular and molecular nature of the niche remains obscure in most SC systems. Our group has been addressing this question using the melanocyte (MC) as a model, because MC SCs (MSCs) and other compartments are distinguished by their location in the hair follicle, the former in the bulge and the other in the hair matrix. On the basis of the gene expression profiles of MSCs, we developed a method to distinguish MSCs from other compartments by using their own characteristics. Using the new criterion for MSCs, we investigated the molecular cues that induce the quiescent MSCs from proliferating melanoblasts. Our study showed that fibroblast growth factor-2 (FGF-2), or an equivalent signal, is essential for inducing a set of MSC signatures, although additional signals required for inducing the ultimate MSCs remain to be identified.