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Yap 控制小鼠出生后表皮中的干细胞/祖细胞增殖。

Yap controls stem/progenitor cell proliferation in the mouse postnatal epidermis.

机构信息

School for Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.

出版信息

J Invest Dermatol. 2013 Jun;133(6):1497-505. doi: 10.1038/jid.2012.430. Epub 2012 Nov 29.

Abstract

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.

摘要

组织更新是皮肤上皮细胞的一个持续过程。我们已经开始研究控制出生后表皮中干细胞/祖细胞激活的遗传机制。保守的 Hippo 通路通过节肢动物到脊椎动物来调节干细胞的更替。在这里,我们表明其下游效应物 yes 相关蛋白 (YAP) 在出生后表皮的干细胞/祖细胞中是活跃的。在转基因小鼠的基底表皮中过表达 C 端截断的 YAP 突变体导致表皮干细胞/祖细胞群体的显著扩张。我们的数据表明,YAP 的 C 端控制了出生后毛囊间表皮中干细胞/祖细胞增殖和分化之间的平衡。我们得出结论,YAP 在表皮中作为干细胞/祖细胞激活的分子开关发挥作用。此外,我们的结果强调了 YAP 作为治疗皮肤癌、银屑病和大疱性表皮松解症等疾病的可能靶点。

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