Pluripotency of induced pluripotent stem cells

An iPS cell is induced from a non-pluripotent cell, but possesses pluripotency similar to that of ES cells. Takahashi and Yamanaka (2006) first achieved this landmark breakthrough by reprograming mouse embryonic fibroblasts (MEFs) into this new type of pluripotent stem cell via the ectopic expression of only four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc. This new procedure circumvented the need for an oocyte, which is required by an earlier method of generating customized pluripotent stem cells termed somatic cell nuclear transfer (SCNT)-mediated nuclear reprogramming [1-3]. Since the discovery of iPS cells, the field has attracted a great amount of scientific and public attention because of the undefined mechanism by which the developmental potential of the cells is reverted and the potential for clinical applications using patient specific iPS cells. The generation of iPS cells from individual patients has raised the hope of treatments for numerous degenerative and genetic diseases [4-11].Unlike normal fertilization or the generation of SCNT-ES cells, the creation of iPS cells is a longer process that results in a heterogeneous mixture of cells with various developmental potentials. In the primary culture, iPS cells are usually present together with the original somatic cells, transformed cells and partially reprogrammed cells. Indeed, iPS cells are only approximately 0.1% to 1% of the total cells used for reprogramming. Moreover, only very small proportions of these cells are fully reprogrammed based on stringent criteria for evaluating pluripotency. Therefore, it is necessary to establish a molecular standard to distinguish fully reprogrammed iPS cells from those that are partially reprogrammed, especially for human iPS cells that may eventually be used for clinical applications.In the present review, we will summarize the most recent progress toward understanding the pluripotency of mouse iPS cells at the functional and molecular levels. We anti