Nobel Prize in Medicine Awarded for Induced Pluripotent Stem Cell Research

The Nobel Prize in Medicine for 2012 has been awarded to Dr. Shinya Yamanka and Sir John Gurdon for their work in induced pluripotent stem-cell (iPS) research. Dr. Yamanka discovered the four transacting factors (OCT4, SOX2, NANOG, and LIN280) in mice which can be used to reprogram cells in order to create iPS cells.

Gurdon discovered in 1962 that the specialization of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.

Shinya Yamanaka later discovered, in 2006, how intact mature cells in mice could be reprogrammed to become immature stem cells by introducing only a few genes. The mature cells could be reprogrammed to become pluripotent stem cells, which are able to develop into all types of cells in the body.

Stem cells have the ability to regenerate tissues that have lost the capacity to repair making them an important and exciting area of research due to the potential applications in medicine. In order to identify the set of factors needed in order to reprogram differentiated cells, mouse fibroblasts were retrovirally transformed using a drug selection cassette (bgeo) that contained both lacZ -galactosidase and neomycin resistance genes under the control of a promoter active only in ES cells (Fbx15). After identifying the minimal set of transcription factors necessary to revert them to an embryonic state, the cells exhibited the morphology and growth properties of ES cells. This data demonstrated that pluripotent stem cells could be generated from fibroblast cultures by the addition of only a few defined factors.

Pluripotent (undifferentiated) stem cells are difficult to maintain because they can easily differentiate in culture and using non-antibody based methods for their isolation is desirable. The undifferentiated stem cell is characterized by high levels of both alkaline phosphatase and aldehyde dehydrogenase. These enzymes can be interrogated in live cells or their extracts by the addition of their fluorogenic substrates, facilitating robust and reliable detection of this valued population of cells.

• Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology 10:622-640.
• Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.