Transient Dux expression facilitates nuclear transfer and induced pluripotent stem cell reprogramming

Cloned animals generated by somatic cell nuclear transfer (SCNT) have been reported for many years; however,SCNTis extremely inefficient, and zygotic genome activation (ZGA) is required forSCNT-mediated somatic cell reprogramming. To identify candidate factors that facilitateZGAinSCNT-mediated reprogramming, we performed siRNA-repressor andmRNA-inducer screenings, which reveal Dux, Dppa2, and Dppa4 as key factors enhancingZGAinSCNT. We show that direct injection ofZGAinducers has no significant effect onSCNTblastocyst formation; however, following the establishment of an inducible Dux transgenic mouse model, we demonstrate that transient overexpression of Dux not only improvesSCNTefficiency but also increases that of chemically induced pluripotent stem cell reprogramming. Moreover, transcriptome profiling reveals that Dux-treatedSCNTembryos are similar to fertilized embryos. Furthermore, transient overexpression of Dux combined with inactivation ofDNAmethyltransferases (Dnmts) further promotes the full embryonic development ofSCNT-derived animals. These findings enhance our understanding ofZGA-regulator function in somatic reprogramming.