Reprogramming of somatic cells to the pluripotent stem cell state may allow the development of in vitro models of disease and could provide a mechanism for the generation of patient-specific cells of therapeutic interest. Reprogramming of mouse fibroblasts into induced pluripotent stem cells, or iPS cells, has been achieved with overexpression of oct4, sox2, klf4, and c-myc and drug selection for the reactivation of a marker of pluripotency (Maherali et al., 2007, Okita et al., 2007, Takahashi and Yamanaka, 2006, Wernig et al., 2007) (reviewed in Yamanaka, 2007). Here we show that n-myc can substitute for c-myc and that drug selection is dispensable for reprogramming of fibroblasts to pluripotent stem cells. We show that serum-free conditions facilitate reprogramming and that the resulting induced pluripotent stem cells contribute extensively to teratomas and chimeras. Our findings greatly simplify the method for induction of pluripotency and bring it one step closer to clinical applications.
