Concise Review: Oct4 and More: The Reprogramming Expressway

Through cellular differentiation, a single cell eventually gives rise to all the various lineages of an organism. This process has traditionally been viewed as irreversible. However, nuclear transfer experiments have demonstrated that differentiated cells can be reprogrammed to form even an entire organism. Yamanaka electrified the world with the discovery that expression of only four transcription factors was sufficient to induce pluripotency in differentiated somatic cells of mammals. Expansion of this work has shown that expression of the master pluripotency gene Oct4 is sufficient to induce pluripotency in neural stem cells. In contrast to somatic cells, germline cells express Oct4 and can acquire pluripotency without the addition of exogenous transcription factors. More recently, it has been possible to also induce an alternative cell fate directly by the transdifferentiation of cells mediated by the introduction of specific transcription factors, including Oct4. Therefore, we suggest that Oct4 is the gatekeeper into a reprogramming expressway that can be directed by altering the experimental conditions. STEM CELLS 2012;30:1521