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

Abstract:

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Larribère L,Galach M,Novak D,Arévalo K,Volz HC,Stark HJ,Boukamp P,Boutros M,Utikal J

doi

10.1016/j.stemcr.2017.08.023

subject

Has Abstract

pub_date

2017-10-10 00:00:00

pages

1234-1245

issue

4

issn

2213-6711

pii

S2213-6711(17)30380-6

journal_volume

9

pub_type

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