The present invention provides a method of altering the differentiative state of cells utilizing innovative protein expression constructs encoding transcription factors. The methods and compositions described herein may be used to generate induced pluripotent stem (iPS) cells, as well as differentiate, transdifferentiate or dedifferentiate cells of various epigenetic status. The method includes introduction of a nucleic acid construct, or expression product thereof, into a cell, and culture of the cell under culture conditions that efficiently converts the cell into a pluripotent cell, enhances the retention of the pluripotent state or efficiently converts the cell into a cell of a cell lineage corresponding to endoderm, mesoderm or ectoderm.
