Induction of pluripotent-like cells derived from MEF by defined factors

Differentiated cells can be reprogrammed to an embryonic-like state by transfer of their nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about the factors that induce this reprogramming. Here we show that the combination of four factors, Oct3/4, Sox2, c-Myc, and Klf4, can generate pluripotent-like stem cells directly from mouse embryonic or adult fibroblast cultures. Unexpectedly, Nanog was dispensable in this process. These cells, which we designated iPS (induced pluriopotent-like stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent-like cells can be directly generated from fibroblast cultures by the addition of only a few defined factors. Keywords: cell type comparison Total RNAs were isolated from indicated cells and labeled with Cy3. Hybridization was performed once for each sample.