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In October 2012, the Nobel Prize in Physiology or Medicine was awarded to two luminaries in the field of reprogramming, Sir John Gurdon of the United Kingdom and Dr. Shinya Yamanaka of Japan. This milestone celebrates a half-century-long paradigm shiftin our understanding of the permanence of cell fate decisions in biology and has important implications for many fields of biomedical research, including research focused on lung injury, repair, and regeneration.
Fifty years ago, as an Oxford graduate student, Gurdon performed his seminal experiment demonstrating that the nucleus of a mature somatic cell, taken from the intestinal epithelium of a tadpole, could be transplanted into an enucleated frog's egg, resetting or reprogramming the cell nucleus into an embryoniclike state able to then develop into a cloned frog (1, 2). These results were controversial at the time, as they demonstrated that development and differentiation are not necessarily one-way, terminal processes but rather can be reversed in the laboratory through the technically demanding feat now known as somatic cell nuclear transfer. Most importantly, Gurdon's experiments settled a long-standing debate over whether a somatic, differentiated cell nucleus retained all the genetic information required to make all the cell types of an organism.
Thirty-five years later, Sir Ian Wilmut replicated Gurdon's technique of somatic cell nuclear transfer to generate Dolly the sheep, proving that reprogramming adult somatic cells was also feasible in mammals (3). Hence, a race was on to discover which proteins or other factors that were contained in the cytoplasm of an egg might be responsible for the phenomenon of nuclear reprogramming. Although some researchers bet that hundreds or thousands of proteins would be required for effective reprogramming, Dr. Shinya Yamanaka, in his typically humble and understated way, announced in 2006 to packed audiences at scientific symposia and in a seminal Cell publication (4) that the transfer of just four transcription factors (Oct4, Sox2, Klf4, and cMyc) into mouse cells could reset the entire epigenetic landscape of a somatic cell, reprogramming it into an embryonic-like pluripotent state virtually identical to that of blastocyst-derived embryonic stem cells. Yamanaka's term "induced pluripotent stem (iPS) cells" is now widely used to refer to the products of his reprogramming methods. In the short 6 years since his discovery, through hundreds of confirmatory...