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A nontransgenic approach to reprogram mouse somatic cells into induced pluripotent stem cells using only small molecules got achieved to propose a potential clinical-friendly cellular reprogramming strategy. Consequently, the screening and identification of small molecules capable of inducing pluripotency genes in human cells are increasingly a focus of research. Because cellular reprogramming is multifactorial in nature, there is a need for versatile small molecules capable of modulating the complicated gene networks associated with pluripotency. We have developed a targeting small molecule called SAHA-PIP comprising the histone deacetylase inhibitor SAHA and the sequence-specific DNA binding pyrrole-imidazole polyamides for modulating distinct gene networks. Here, we report the identification of a SAHA-PIP termed Ì that could trigger genome-wide epigenetic reprogramming and turn ON the typically conserved core pluripotency gene network. Through independent lines of evidence, we report for the first time a synthetic small molecule inducer that target and activate the OCT-3/4 regulated pluripotency genes in human dermal fibroblasts.

Original publication




Journal article


ACS Chem Biol

Publication Date





2729 - 2736


Animals, Biomarkers, Cell Differentiation, Cells, Cultured, Cellular Reprogramming, Chromatin, Epigenesis, Genetic, Fibroblasts, Gene Expression Profiling, Gene Regulatory Networks, Histone Deacetylase Inhibitors, Humans, Induced Pluripotent Stem Cells, Mice, Molecular Structure, Nylons, Octamer Transcription Factor-3, Pyrroles, Small Molecule Libraries