Yap Controls Stem/Progenitor Cell Proliferation in the Mouse Postnatal Epidermis
Yap Controls Stem/Progenitor Cell Proliferation in the Mouse Postnatal Epidermis
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DOI：
10.1038/jid.2012.430
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发表时间：
2013-06-01
影响因子：
6.5
通讯作者：
Key, Brian
中科院分区：
文献类型：
--
作者：
Beverdam, Annemiek;Claxton, Christina;Key, Brian
组织更新是皮肤上皮中的持续过程。我们已经开始研究控制出生后表皮中干/祖细胞激活的遗传机制。保守的Hippo途径调节节肢动物至脊椎动物的干细胞更新。在这里，我们表明，其下游效应，是相关蛋白（雅普），是活跃的干/祖细胞的出生后表皮。在转基因小鼠的基底表皮中C-末端截短的雅普突变体的过表达引起表皮干/祖细胞群体的显著扩增。我们的数据表明，C-末端的雅普控制干/祖细胞增殖和分化之间的平衡，在出生后的毛囊间表皮。我们的结论是，雅普的功能作为一个分子开关的干/祖细胞活化的表皮。此外，我们的研究结果强调雅普作为一个可能的治疗靶点的疾病，如皮肤癌，银屑病，和大疱性表皮。
Tissue renewal is an ongoing process in the epithelium of the skin. We have begun to examine the genetic mechanisms that control stem/progenitor cell activation in the postnatal epidermis. The conserved Hippo pathway regulates stem cell turnover in arthropods through to vertebrates. Here we show that its downstream effector, yes-associated protein (YAP), is active in the stem/progenitor cells of the postnatal epidermis. Overexpression of a C-terminally truncated YAP mutant in the basal epidermis of transgenic mice caused marked expansion of epidermal stem/progenitor cell populations. Our data suggest that the C-terminus of YAP controls the balance between stem/progenitor cell proliferation and differentiation in the postnatal interfollicular epidermis. We conclude that YAP functions as a molecular switch of stem/progenitor cell activation in the epidermis. Moreover, our results highlight YAP as a possible therapeutic target for diseases such as skin cancer, psoriasis, and epidermolysis bullosa.