Abstract
Recent studies have demonstrated that differentiated somatic cells from various mammalian species can be reprogrammed into induced pluripotent stem (iPS) cells by the ectopic expression of four transcription factors that are highly expressed in embryonic stem (ES) cells. The generation of patient-specific iPS cells directly from somatic cells without using oocytes or embryos holds great promise for curing numerous diseases that are currently unresponsive to traditional clinical approaches. However, some recent studies have argued that various iPS cell lines may still retain certain epigenetic memories that are inherited from the somatic cells. Such observations have raised concerns regarding the safety and efficacy of using iPS cell derivatives for clinical applications. Recently, our study demonstrated full pluripotency of mouse iPS cells by tetraploid complementation, indicating that it is possible to obtain fully reprogrammed iPS cells directly from differentiated somatic cells. Therefore, we propose in this review that further comprehensive studies of both mouse and human iPS cells are required so that additional information will be available for evaluating the quality of human iPS cells.
Highlights
An induced pluripotent stem (iPS) cell is induced from a non-pluripotent cell, but possesses pluripotency similar to that of embryonic stem (ES) cells
We suggest that a comprehensive comparison of DNA methylation, gene expression and non-coding RNAs using mouse iPS cell lines derived from the same somatic cells with varying developmental potentials would provide a greater understanding of the regulation of pluripotency
We propose that the minimum requirements for the clinical use of human iPS cells are: 1) a normal karyotype, because some sub-karyotypic alterations are observed during reprogramming and a normal karyotype is an important factor for ES cell characterization; 2) a normal genotype
Summary
An iPS cell is induced from a non-pluripotent cell, but possesses pluripotency similar to that of ES cells. It is not practical to differentiate pluripotent stem cells into all of the possible cell types of an organism in vitro, an embryoid body (EB) that forms the three germ layers can be induced. Functional Evaluation of Mouse iPS Cell Pluripotency The landmark achievement by Takahashi and Yamanaka revealed that ectopic expression of four transcription factors in differentiated MEFs can induce nuclear reprogramming to form iPS cells with a typical ES cell morphology.
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