Department of Stem Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Cell Stem Cell. 2010 Feb 5;6(2):130-40. doi: 10.1016/j.stem.2009.12.010.
Melanocyte stem cells in the bulge area of hair follicles are responsible for hair pigmentation, and defects in them cause hair graying. Here we describe the process of melanocyte stem cell entry into the quiescent state and show that niche-derived transforming growth factor beta (TGF-beta) signaling plays important roles in this process. In vitro, TGF-beta not only induces reversible cell cycle arrest, but also promotes melanocyte immaturity by downregulating MITF, the master transcriptional regulator of melanocyte differentiation, and its downstream melanogenic genes. In vivo, TGF-beta signaling is activated in melanocyte stem cells when they reenter the quiescent noncycling state during the hair cycle and this process requires Bcl2 for cell survival. Furthermore, targeted TGF-beta type II receptor (TGFbRII) deficiency in the melanocyte lineage causes incomplete maintenance of melanocyte stem cell immaturity and results in mild hair graying. These data demonstrate that the TGF-beta signaling pathway is one of the key niche factors that regulate melanocyte stem cell immaturity and quiescence.
毛囊隆突区的黑素细胞干细胞负责毛发的色素形成，而这些细胞的缺陷会导致毛发变白。本文描述了黑素细胞干细胞进入静止状态的过程，并表明龛源转化生长因子β（TGF-β）信号在这个过程中发挥着重要作用。体外实验表明，TGF-β不仅诱导细胞周期的可逆性停滞，还通过下调 MITF 及其下游的黑色素生成基因，促进黑素细胞不成熟。在体内，当黑素细胞干细胞在毛发周期中重新进入静止的非循环状态时，TGF-β信号会在其内部被激活，而这个过程需要 Bcl2 来维持细胞的存活。此外，靶向敲除黑素细胞谱系中的 TGF-β Ⅱ型受体（TGFbRII）会导致黑素细胞干细胞不成熟的维持不完全，从而导致轻微的毛发变白。这些数据表明，TGF-β信号通路是调节黑素细胞干细胞不成熟和静止状态的关键龛位因子之一。
