申请人前期工作发现成熟垂体损伤后具有再生功能：转基因诱导垂体损伤小鼠（GHCre/iDTR）模型中，特异性诱导生长激素（GH+））细胞凋亡后，干细胞（Sox2+）在其微环境即垂体前、中叶边缘大量增殖，随后垂体实质内损伤部位的内分泌细胞逐渐得到补充。这一发现提示了干细胞在微环境激活增殖后,可能通过上皮-间叶样转换（EMT）获得迁移能力而迁移到损伤部位，分化成缺失细胞。干细胞基因谱分析初步证实了这一推测：与对照组相比，大量EMT诱导因子及下游调控因子和间叶样细胞标记物在再生垂体干细胞中有明显上调，而上皮细胞相关基因却有明显下调。本项目以上述结果为依托，运用可控垂体损伤及干细胞eGFP标记可控垂体损伤小鼠模型，通过SP干细胞分离，活细胞实时监测等实验手段，验证EMT在垂体再生中对干细胞的调节，重点在细胞，组织及整体水平探索其调控机制，为干细胞治疗在垂体的运用提供重要的依据。

In recent studies, we showed that the adult pituitary is capable of repairing injury; growth hormone-producing (GH+) somatotropes are regenerated after transgenically induced ablation using GHCre/iDTR mice, mainly driven by stem cell activation and differentiation. Quite interestingly, stem cells (Sox2+), which are particularly expanded in the stem cell niche after pituitary injury, showed a trend of migration from stem cell niche (marginal zone layer of anterior and intermediate lobe) to injury sites in parenchyma, indicating the involvement of epithelial-mesenchymal transition (EMT), a transition process that cells are able to acquire migration and invasion ability. Moreover, this phenomenon is strongly supported by our preliminary whole-genome expression analysis data that a number of EMT inducers and downstream regulators and of mesenchymal markers are upregulated in the stem/progenitor cell compartment of regenerating pituitary while some epithelial-related genes are downregulated when compare to control pituitary. In this proposal, we would like to further investigate the effect of EMT in regulating stem cell function during pituitary remodeling, and mainly focus on searching for the molecular mechanism underlying this phenomenon. Exploration may lead to clinical opportunities for stem cell therapy in plenty of tissues.