A Combined Chemical and Genetic Approach for the Generation of Induced Pluripotent Stem Cells

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

“…In addition, Maekawa et al [49] have shown that the Glis family zinc finger 1 protein Glis1 can substitute cMyc in the reprogramming cocktail by inducing MET, thus initiating iPS cell reprogramming. MET can also be induced by chemicals, for example, various groups have demonstrated the ability of transforming growth factor (TGF)β inhibition to enhance the initiation stage of both mouse [50,51] and human [42] somatic cell reprogramming. This observation is supported by the finding that addition of recombinant TGFβ abrogates iPS cell formation [42] and is likely due to the EMTinducing action of TGFβ signalling, which then prevents the MET that is critical to successful iPS cell reprogram-…”

“…Histone methyltransferase inhibitor Shi et al [51] Bayk8644 Calcium channel agonist Shi et al [51] RG108 DNA methyltransferase inhibitor Shi et al [51] 5-Aza-2'-Deoxycytidine DNA methyltransferase inhibitor Huangfu et al [89] Dexamethasone Steroid glucocorticoid Huangfu et al [89] Valproic acid HDAC inhibitor Huangfu et al [89] Trichostatin A HDAC inhibitor Huangfu et al [89] SAHA HDAC inhibitor Huangfu et al [89] PD0325901 + CHIR99021…”

“…MAPK inhibition and GSK3 inhibition Shi et al [51] , Silva et al [77] SB 431542+ PD0325901 TGFβ inhibitor Lin et al [42] And MAPK inhibitor A-83-01…”

Generation of Induced Pluripotent Stem Cell Lines from Tibetan Miniature Pig

“…However, before jumping onto such extraordinary endeavor, safety must be scrupulously tested in an animal model close enough to humans. Nowadays that iPS technology is expanding, with improved delivery systems, chemical additions, new tissue culture conditions, and multiple cell sources being reported regularly, such animal model is essential to set up quality standards (12)(13)(14)(15)(16)(17)(18). Mice, and maybe rats, will possibly continue unrivalled as the easier ways to learn about reprogramming machinery and improve methodology, but their size, physiology, and reduced lifespan are handicaps for making serious assumptions regarding safety in humans.…”

JHDM3A Module as an Effector Molecule in Guide-directed Modification of Target Chromatin

“…Fundamental changes in the nature of cells generally stem from perturbations in the transcriptional regulatory machinery; for example, changes in DNA methylation states at the regulatory DNA regions, mutations in chromatin remodeling complexes such as SWI/SNF, and/or changes in post-translational modifications of histone tails (4). Attempts to modulate DNA methylation by DNA methyltransferase inhibitors (5,6), histone deacetylation by HDAC inhibitors (7)(8)(9), and histone methylation by histone demethylase inhibitors (10,11) have received a great deal of attention. However, treating cells with small molecules such as these can lead to total inactivation of the target proteins, which could cause a chaotic alteration of epigenetic states by influencing the chromatin in its entirety and driving it to a structurally and functionally disorganized state.…”