Inhibitory Smad proteins promote the differentiation of mouse embryonic stem cells into ependymal-like ciliated cells

Motile cilia play crucial roles in the maintenance of homeostasis in vivo. Defects in the biosynthesis of cilia cause immotile cilia syndrome, also known as primary ciliary dyskinesia (PCD), which is associated with a variety of complex diseases. In this study, we found that inhibitory Smad proteins, Smad7 and Smad6, significantly promoted the differentiation of mouse embryonic stem (ES) cells into ciliated cells. Moreover, these Smad proteins specifically induced morphologically distinct Musashi1-positive ciliated cells. These results suggest that inhibitory Smad proteins could be important regulators not only for the regulation of ciliated cell differentiation, but also for the subtype specification of ciliated cells during differentiation from mouse ES cells.

Research highlights
► Morphologically distinct two types of ciliated cells can be induced from mouse ES cells.
► Smad7 and Smad6 significantly promote the differentiation of mouse ES cells into ciliated cells.
► These inhibitory Smad proteins specifically promote Musashi1-positive ependymal-like cells.