Transgenic Mice with Defined Combinations of Drug Inducible Reprogramming Factors

Drug-inducible lentiviruses encoding Oct4, Sox2, Klf4 and c-Myc were used to derive “primary” iPS cells and segregated through germline transmission generating mice and fibroblasts carrying subsets of the reprogramming factors. Drug treatment of the cells resulted in “secondary” iPS cell derivation only when the missing factor was introduced. This creates a defined platform for studying reprogramming mechanisms and allows screening of genetically homogenous cells for compounds that replace any transcription factor required for iPS cell derivation.