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Unraveling Epigenetic Regulation in Embryonic Stem Cells

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1 Unraveling Epigenetic Regulation in Embryonic Stem Cells
Marina Bibikova, Louise C. Laurent, Bing Ren, Jeanne F. Loring, Jian-Bing Fan  Cell Stem Cell  Volume 2, Issue 2, Pages (February 2008) DOI: /j.stem Copyright © 2008 Elsevier Inc. Terms and Conditions

2 Figure 1 Comprehensive Epigenetic Characterization of ES Cells at Multiple Molecular Levels ChIP-chip, chromatin immunoprecipitation followed by microarray (i.e., chip) readout; ChIP-Seq, chromatin immunoprecipitation followed by sequencing readout; MeDIP, methylated DNA immunoprecipitation; DGE, digital gene expression. Cell Stem Cell 2008 2, DOI: ( /j.stem ) Copyright © 2008 Elsevier Inc. Terms and Conditions

3 Figure 2 Model Illustrating the Contribution of Four Epigenetic Regulatory Mechanisms to Stabilization of Cellular States This schematic represents possible transitions between cellular differentiation states, including pluripotent cells, lineage-specific progenitor cells, intermediate cells in specific lineages, and fully differentiated cells. Stable differentiation states are depicted as potential energy wells, while the transitions between them are potential energy barriers. We postulate that crosstalk between different regulatory mechanisms (transcription factors, DNA methylation [Me-DNA], miRNAs, and histone marks) stabilize each of these differentiation states. Perturbations of one or more of these mechanisms can overcome the potential energy barriers between states. Examples of transitions: in vivo differentiation of pluripotent cells → progenitor cells → differentiated cells (yellow arrows); in vitro manipulation of transcription factors resulting in mES cells → trophoblast stem cells (Niwa et al., 2000, 2005) (blue arrow); fibroblasts → iPS cells (Okita et al., 2007; Takahashi and Yamanaka, 2006; Wernig et al., 2007) (green arrow); and transdifferentiation (hypothetical, red arrow). Cell Stem Cell 2008 2, DOI: ( /j.stem ) Copyright © 2008 Elsevier Inc. Terms and Conditions


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