Skin Cancer Unit (G300), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69121 Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Skin Cancer Unit (G300), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69121 Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Stem Cell Reports. 2017 Oct 10;9(4):1234-1245. doi: 10.1016/j.stemcr.2017.08.023. Epub 2017 Sep 28.
Molecular mechanisms responsible for the development of human skin epithelial cells are incompletely understood. As a consequence, the efficiency to establish a pure skin epithelial cell population from human induced pluripotent stem cells (hiPSCs) remains poor. Using an approach including RNAi and high-throughput imaging of early epithelial cells, we identified candidate kinases involved in their differentiation from hiPSCs. Among these, we found HIPK4 to be an important inhibitor of this process. Indeed, its silencing increased the amount of generated skin epithelial precursors at an early time point, increased the amount of generated keratinocytes at a later time point, and improved growth and differentiation of organotypic cultures, allowing for the formation of a denser basal layer and stratification with the expression of several keratins. Our data bring substantial input regarding regulation of human skin epithelial differentiation and for improving differentiation protocols from pluripotent stem cells.
人类皮肤上皮细胞发育的分子机制尚不完全清楚。因此，从人诱导多能干细胞（hiPSCs）中建立纯皮肤上皮细胞群体的效率仍然很低。我们采用包括 RNAi 和高通量成像早期上皮细胞的方法，鉴定了参与 hiPSC 分化的候选激酶。其中，我们发现 HIPK4 是该过程的重要抑制剂。事实上，沉默 HIPK4 会增加早期产生的皮肤上皮前体的数量，增加后期产生的角质细胞的数量，并改善器官型培养物的生长和分化，形成更密集的基底细胞层和分层，并表达多种角蛋白。我们的数据为人类皮肤上皮细胞分化的调控以及从多能干细胞改善分化方案提供了重要的依据。
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