microRNA92a通过decorin/TGF-β通路调控早期毛囊发育的机制研究

Multipotent progenitors within the single-layered surface epithelium differentiate and form the epidermis and follicles during embryogenesis. Recently, more and more attentions have been drew with the character of microRNAs (miRNAs) in skin morphogenesis. Our prior study found that, decorin, which regulates bulge stem cell niche, prolonged follicular anagen by the regulation of tumor growth factor-β (TGF-β) signaling. Recently, our research unveil that miR92a is selectively expressed within the follicular epithelial cell compartments during early follicular morphogenesis by microarray and in situ hybridization (ISH). Decorin is also highly expressed within the follicular epithelial compartments. However, there has been no research on the regulation in follicular morphogenesis of miR92a and decorin. We aim to over-express or inhibit miR92a in the embryonic epithelial progenitors from C57/BL mouse or miR92a-transgenic mouse, add decorin in the progenitors, and use the miR92a-transgenic mouse model to explore the regulation of miR92a in cellular functions of multi-potential embryonic epithelial progenitors and its regulation in early embryonic follicular lineage fate decision and morphogenesis via decorin/TGF-β signaling. Our study may provide theory foundations for the feasibility of constructing seed cells of tissue engineer using miR92a.

表皮及毛囊均由胚胎发育中的外胚层单层多潜能上皮祖细胞分化形成，microRNAs对早期皮肤发育的调节已日益引人关注。我们前期研究发现参与毛囊干细胞Niche组成的decorin可以通过调控TGF-β通路延长毛囊生长期。新近，我们应用microarray及原位杂交等技术发现miR92a在C57/BL小鼠早期胚胎发育中的毛囊上皮选择性高表达，decorin在这些上皮结构中也高表达，但两者在早期毛囊发育中的相互作用目前尚未知。本项目拟通过在C57/BL小鼠或miR92a转基因小鼠胚胎源上皮祖细胞中导入或抑制miR92a，加入decorin的体外模型研究，以及miR92a转基因小鼠模型的研究，探讨miR92a通过decorin/TGF-β通路调控胚胎期多潜能上皮祖细胞的功能，进而调控胚胎期毛囊谱系分化及早期毛囊发育的作用。我们的研究将为探索利用miR92a构建组织工程种子细胞的可行性提供理论依据。

表皮及毛囊均由胚胎发育中的外胚层单层多潜能上皮祖细胞分化形成，microRNAs对早期皮肤毛囊发育的调节已日益引人关注。本项目通过体外细胞模型处理研究发现，在C57/BL小鼠上皮源细胞及人头皮外根鞘细胞中过表达miR92a能通过调控Wnt通路参与细胞功能调控。通过decorin过表达转基因小鼠模型研究发现，decorin过表达能通过调控小鼠毛囊干细胞（HFSC)静止/活化平衡推迟小鼠发育期进入第一休止期。而通过miR17-92 cluster在HFSC区域特异性敲除小鼠模型的研究，发现在HFSC中敲除miR17-92 cluster也能显著促进小鼠出生后毛囊由休止期进入生长期。我们的研究将为探索利用miRNAs构建组织工程种子细胞的可行性提供理论依据。