Induced Pluripotent Stem Cell Lines Derived From Human Somatic Cells

Epigenetic Modifications and Stem Cell Toxicology: Searching for the Missing Link

“…Conserved RNA-binding protein that is highly expressed in mouse and human embryonic stem cells; used experimentally to augment generation of iPS cells from human fibroblasts (Yu et al, 2007) c-Myc Implicated in stem cell self-renewal and differentiation, specifically in the interaction between stem cells and the local microenvironment; modulates an assortment of other cellular functions, such as cell cycle regulation, differentiation, and metabolism (Murphy, Wilson, and Trumpp, 2005) methylation is linked to transcriptional repression by endorsing a compact chromatin structure (Ringrose, Ehret, and Paro, 2004). ES cells harbor a novel chromatin modification pattern, termed bivalent domains, that contains large regions of Lys27 methylation and smaller regions of Lys4 methylation (Bernstein et al, 2006).…”

“…Regulating the transcriptional expression network is pivotal as a means to maintain self-renewal and pluripotency of ES cells and as a method to display the full therapeutic potential of these cells. Reprogramming of fibroblasts to pluripotent stem cells can be stimulated in vitro by the ectopic expression of the following set of TFs: (i) Oct4, Sox2, c-Myc, and Klf4 (Takahashi et al, 2007); (ii) Oct4, Sox2, Nanog, and Lin-28 (Yu et al, 2007); and (iii) Oct4, Nanog, Sox2, Lin-28, c-Myc, and Klf4 (Liao et al, 2008).…”

Cardiac Toxicity

“…All patch clamp experiments including the current recordings were conducted with the automated planar patch clamp systems Port-a-Patch and Patchliner from Nanion (Munich, Germany) allowing the assessment of the modulation of cardiac repolarization in a higher throughput. The identification of methods aimed at reprogramming of the human somatic cells to so-called induced pluripotent stem (iPS) offers the possibility to generate tailormade human cardiomyocytes that will most probably allow the development of ethnical or disease-specific drug actions on cardiomyocytes [68,69].…”

“…Generation of the mouse ES cell line D3 and their differentiation into cardiac myocytes was published in 1985 by Doetschman et al [100]. Almost 20 years later the generation of human ES cells and differentiation into cardiomyocytes were described [101,102], followed by the recent development of human-induced pluripotent stem cells [68,69]. The usefulness, relevance, and predictivity of stem cell-derived cardiomyocytes as well as other cell types for determination of drug-induced toxicity have been well recognized during the past years (for review, [103][104][105]).…”

Colorectal Cancer Stem Cells

“…Recently, Oct-4 has also been identified as one of four transcriptional factors that can induce pluripotent stem cells from adult human fibroblasts. 37,38 It is feasible that normally differentiated cells could undergo transformation and develop dysregulated self-renewal properties with reactivation of these transcriptional factors. Oct-4 is controlled by Hif-2a, a transcriptional factor that is expressed in hypoxia.…”