tem cells are a distinct self-replenishing cell population whose primary function is to generate progeny that then develop into terminally differentiated cell types, such as a cardiomyocytes, neurons or photoreceptors. Tissuespecific adult stem cells, or progenitors, are committed to producing tissue or lineage-specific cells, whereas totipotent or pluripotent stem cells can give rise to any of the 200+ cell types of the body. There are two types of pluripotent stem cells defined by their tissue origin: 1) embryonic stem (ES) cells obtained from early embryos, typically at the blastula stage, and 2) induced pluripotent stem (iPS) cells derived through a reprogramming process whereby terminally differentiated somatic cells are reprogrammed or induced to a pluripotent state (Figure 1).
Successful generation of human iPS cells was reported independently in 2007 by the research groups of Drs James Thomson and ShinyaYamanaka 1,2 . Both groups successfully identified a minimum number of nuclear factors that could reprogramme terminally differentiated fibroblasts to pluripotent cell lines by exogenously expressing distinct yet overlapping sets of genes: Yu and colleagues used Oct4, Sox2, Nanog and Lin28 by lentiviral gene transfer, while Yamanaka and colleagues employed Oct4, Sox2, Klf4 and c-Myc via retroviral gene transfer. These landmark studies were a significant advance over whole nucleus reprogramming 3 and have had several important consequences. Induced pluripotent stem cell technology does not require human embryos and thus circumvents the ethical issues associated with