arima masaru

Hair follicle stem cells (HFSC) are localized in the bulge region of the hair follicle and play a role in producing hair. Recently, it has been shown that the number of HFSC decreases with age, which is thought to be a cause of senile alopecia. Therefore, maintaining HFSC may be key for the prevention of age-related hair loss, but the regulatory mechanisms of HFSC and the effects of aging on them are largely unknown. In general, stem cells are known to require regulatory factors in the pericellular microenvironment, termed the stem cell niche, to maintain their cell function. In this study, we focused on the extracellular matrix proteoglycan decorin (DCN) as a candidate factor for maintaining the human HFSC niche. Gene expression analysis showed that DCN was highly expressed in the bulge region. We observed decreases in DCN expression as well as the number of KRT15-positive HFSC with age. In vitro experiments with human plucked hair-derived HFSC revealed that HFSC lost their undifferentiated state with increasing passages, and prior to this change a decrease in DCN expression was observed. Furthermore, knockdown of DCN promoted HFSC differentiation. In contrast, when HFSC were cultured on DCN-coated plates, they showed an even more undifferentiated state. From these results, as a novel mechanism for maintaining HFSC, it was suggested that DCN functions as a stem cell niche component, and that the deficit of HFSC maintenance caused by a reduction in DCN expression could be a cause of age-related hair loss.

Interfollicular epidermal stem cells (IFE-SCs) have self-renewal and differentiation potentials, and maintain epidermal homeostasis. Stem cells in vivo are regulated by the surrounding environment called niche to function properly, however, IFE-SC niche components are not fully understood. In order to elucidate the mechanisms of keeping epidermal homeostasis and of skin aging, and also to develop new therapeutic technologies for skin diseases, we searched for niche factors that regulate IFE-SCs. We found that laminin-332, a basement membrane component, was highly expressed at the tips of the dermal papillae, where IFE-SCs are localized, and that the stem cells by themselves expressed laminin-332. Knockdown of laminin-332 during the culture of IFE-SC-model cells to construct 3-dimensional epidermis in vitro resulted in failure to form proper structure, although no significant change was observed in either cell growth or apoptosis. Pre-coating of the culture insert with laminin-332 restored the normal formation of 3-dimensional epidermis. From these results, it was shown that laminin-332 is an essential niche component for the proper differentiation of IFE-SCs.