Identification of a Small Molecule That Turns ON the Pluripotency Gene Circuitry in Human Fibroblasts

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• 作者：Ganesh N. Pandian ; Shinsuke Sato ; Chandran Anandhakumar ; Junichi Taniguchi ; Kazuhiro Takashima ; Junetha Syed ; Le Han ; Abhijit Saha ; Toshikazu Bando ; Hiroki Nagase ; Hiroshi Sugiyama
• 刊名：ACS Chemical Biology
• 出版年：2014
• 出版时间：December 19, 2014
• 年：2014
• 卷：9
• 期：12
• 页码：2729-2736
• 全文大小：456K
• ISSN：1554-8937

文摘

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 I虁 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.