An RNAi Screen Reveals an Essential Role for HIPK4 in Human Skin Epithelial Differentiation from iPSCs

• Main Authors: Lionel Larribère, Marta Galach, Daniel Novak, Karla Arévalo, Hans Christian Volz, Hans-Jürgen Stark, Petra Boukamp, Michael Boutros, Jochen Utikal
• Format: Article
• Language: English
• Published: Elsevier 2017-10-01
• Series: Stem Cell Reports
• Subjects: keratinocytes; iPSC; HIPK4; differentiation; RNAi screen; epithelium; skin; stem cell; organotypic culture; development
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213671117303806

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.