title: Identification of a small molecule that turns ON the pluripotency gene circuitry in human fibroblasts.
abstract: 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.
authors.affiliation: Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University , Sakyo, Kyoto 606-8502, Japan.
authors.forename: Ganesh N
authors.initials: GN
authors.lastname: Pandian
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sato
authors.forename: Chandran
authors.initials: C
authors.lastname: Anandhakumar
authors.forename: Junichi
authors.initials: J
authors.lastname: Taniguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takashima
authors.forename: Junetha
authors.initials: J
authors.lastname: Syed
authors.forename: Le
authors.initials: L
authors.lastname: Han
authors.forename: Abhijit
authors.initials: A
authors.lastname: Saha
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009757:Nylons / Q000138:chemical synthesis / Q000494:pharmacology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D009757:Nylons; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011758:Pyrroles; C585734:SAHA-PIP-delta; D054852:Small Molecule Libraries