Methods and composition of induction of pluripotent stem cells are disclosed. For example, in certain aspects methods for generating essentially vector-free induced pluripotent stem cells with cell signaling regulators are described. Furthermore, certain aspects of the invention provide novel compositions comprising induced pluripotent stem cells essentially free of exogenous retroviral vector elements in the presence of a medium comprising signaling inhibitors. In certain aspects, feeder-free episomal reprogramming methods may be provided.
