al., 2004), and randomly integrated promoters are often subject to positional effects that can strongly limit their activity (Zafarana et al., 2009). Differentiation further increases the chances of silencing, as transgenes can be located in regions where heterochromatin forms following cell fate choices (Herbst et al., 2012; Raya et al., 2009). As a consequence, inducible shRNA expression in both hPSCs and a wide variety of their differentiated progenies has never been reported.