MicroRNAs (miRNAs) are emerging critical regulators of cellfunction that frequently reside in clusters throughout the genome. They influence amyriad of cellfunctions, including the generation of induced pluripotent stem cells, also termed reprogramming. Here, we have successfully delivered entire miRNA clusters into reprogrammingfibroblasts using retroviral vectors. This strategy avoids caveats associated with transient transfection of chemically synthesized miRNA mimics. Overexpression of 2 miRNA clusters, 106a-363 and in particular 302- 367, allowed potent increases in induced pluripotent stem cellgeneration efficiency in mouse fibroblasts using 3 exogenous factors (Sox2, Klf4, and Oct4). Pathway analysis highlighted potential relevant effectors, including mesenchymal- to- epithelial transition, cellcycle, and epigenetic regulators. Further study showed that miRNA cluster 302- 367targeted TGF beta receptor 2, promoted increased E-cadherin expression, and accelerated mesenchymal- to- epithelialchanges necessary for colony formation. Our work thus provides an interesting alternative for improving reprogrammingusing miRNAs and adds new evidence for the emerging relationship between pluripotency and the epithelialphenotype.