Stable transgene expression remains challenging during human pluripotent stem cell differentiation. Wernig and colleagues show that combining CAG/Ubc promoters with WPRE prevents transgene silencing following both random and targeted integration. This work provides a broadly applicable genetic tool for studies requiring sustained transgene expression during differentiation of pluripotent stem cells.

While high and stable transgene expression can be achieved in undifferentiated pluripotent stem cells, conventional transgene expression systems are often silenced upon differentiation. Silencing occu...