Abstract IA12: Induction of pluripotency by defined factors

Abstract

Abstract Induced pluripotent stem (iPS) cells were originally generated from mouse and human fibroblasts by the retroviral introduction of Oct3/4, Sox2, c-Myc, and Klf4. iPS cells are similar to embryonic stem (ES) cells in morphology, proliferation, gene expression, and most importantly, pluripotency. Patient-specific iPS cells provide us with unprecedented opportunities in disease research, drug screening, toxicology, and cell transplantation therapies. Banks of iPS cells from individuals with HLA homozygous alleles may also provide another unprecedented source for regenerative medicine. iPS cells have many variations in comparison to ES cells. In addition to fibroblasts, iPS cells can be generated from various somatic cells, such as hepatic cells, gastric epithelial cells, keratinocytes, neural cells, peripheral blood cells, and cord blood cells. In addition to retroviral transduction, iPS cells can be integration-freely generated by adenoviruses, sendaiviruses, plasmids, transposons, recombinant proteins, and synthetic mRNA. Several chemicals and inhibitors have been shown to enhance iPS cell generation. Some of the original four factors can either be omitted or replaced by other genes or chemicals. Finally, each induction experiment can result in 100 or more independent iPS cell clones. These various iPS cells may vary significantly in regard to each cell's peculiar characteristics, such as the efficacy of in vitro directed differentiation and a propensity to produce tumors. In fact, the origins of iPS cells have a profound effect on their tumorigenicity. It is therefore necessary to determine the best origins, the best induction protocols, and the best methods to evaluate iPS cell clones and subclones for each application of iPS cells. Here, significance of epigenome analyses, including methylome, histone modifications, and imprinting increases as the integration-free method is becoming practical. It is also important to note that an iPS cell clone can be heterogeneous despite the fact that all the cells within the clone are derived from a single progenitor cell. This is because the process requires multiple cell divisions which cannot be completed by the four exogenous factors alone. Additional factors including p53 and Rb pathways are considered to play various roles in achieving full reprogramming. Obtaining a better understanding of the reprogramming mechanisms will therefore facilitate the generation of more uniform iPS cells in the future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA12.