共栖状态下毛囊干双向调控黑素干激活的实验研究

The coexistence of different kind of stem cells in the niche is a new scientific question in stem cell biology, and the mammalian hair follicle, containing two stem cell populations, namely epithelial stem cells of hair follicle(EpSCHFs) and melanocyte stem cells of hair follicle(McSCHFs) in Bulge area, serves as an advantageous model for the dissection of such coexistence and interaction among distinct cell types. EpSCHFs may impact McSCHFs intimately and then they both together undergo differentiation and proliferation to regenerate pigmented hair, and Wnt signaling pathway plays an important role in this processes. However, the mechanisms behind these coordinated and interacted stem cell behaviors have not been elucidated. In previous works, we identified several Wnt molecules as key signals that functioned in coupling the behavior of the two stem cells. In this study, focusing on the transforming inflexion of quiescence-activation of McSCHFs within the Bulge in hair growth cycle and using genetic mouse models and co-cultured systems of both stem cells, we hope to show the possibility that the identified 2 groups of Wnt signals originated from the paracrine of EpSCHFs initiate the onset of activation of McSCHFs and drive their differentiation into pigment-producing melanocytes, and we hope to confirm our hypothesis that the differentiation regulation McSCHFs by EpSCHFs is in bidirectional way,namely the positive regulation via canonical Wnt pathway and the negative control via non-canonical Wnt pathway respectively. This study not only may define the roles for Wnt signaling in the regulation of McSCHFs but also may illustrate mechanisms for coexistence of stem cells involved in the different organs in adult mammals.

干细胞自身的性质功能与其栖息的干细胞巢密不可分，巢内实质性组分及各种因子共同构成了干细胞的功能调控网络，其中，巢内不同种类的干细胞的共栖状态和相互作用可能具有重要的意义。本项目研究毛囊Bulge巢内毛囊干和黑素干共栖状态下，黑素干被毛囊干旁分泌的Wnt信号诱导激活并进入初始分化的可能性，拟证明：毛囊干和黑素干的同巢共栖具有重要的生物学意义，黑素干的分化命运决定与此密切关联；毛囊干旁分泌特定的Wnt分子是黑素干的"静息-激活"转换的重要因素，经此，毛囊干可对黑素干的激活进行正负双向的调控。希望本课题结果能为成体干细胞巢内不同种类的干细胞共栖及相互作用的研究提供基础。