Induced pluripotent stem cells (iPSCs) have been produced from a number of mouse and human somatic cell types upon the enforced expression of the transcription factors (TF) Oct4, Klf4, Sox2, and c-Myc (OKSM). These cells are able to generate any cell lineage and are therefore important to understand development. Further, they can potentially be used in cell therapy, drug screening and disease modelling. Cells undergoing reprogramming initially downregulate the fibroblast-associated marker Thy1, then activate the SSEA1 antigen and eventually express Oct4, before forming stable iPSC colonies after 15 days. We have defined two different populations during reprogramming. One population, which is SSEA1+, can form iPSCs, and the other is refractory cells, which include both Thy1+ and Thy1– , that are not able to form iPSC. In an attempt to rescue Thy1+ cells, Thy1+ cells at different stages of reprogramming (days 3, 6, 9, and 12) were infected with lentiviral vectors expressing additional copies of OKSM. As a result Thy1+ cells with extra copies of OKSM were able to form iPS colonies, but not the untreated control cells. This data demonstrated that the inability to sustain OKSM protein expression in Thy1+ cells on or after day 3 broadly contributed to their failure to form iPSCs.