title: Brief Report: Inhibition of miR-145 Enhances Reprogramming of Human Dermal Fibroblasts to Induced Pluripotent Stem Cells.
abstract: MicroRNA (miRNAs) are short noncoding RNA molecules involved in many cellular processes and shown to play a key role in somatic cell induced reprogramming. We performed an array based screening to identify candidates that are differentially expressed between dermal skin fibroblasts (DFs) and induced pluripotent stem cells (iPSCs). We focused our investigations on miR-145 and showed that this candidate is highly expressed in DFs relative to iPSCs and significantly downregulated during reprogramming process. Inhibition of miR-145 in DFs led to the induction of "cellular plasticity" demonstrated by: (a) alteration of cell morphology associated with downregulation of mesenchymal and upregulation of epithelial markers; (b) upregulation of pluripotency-associated genes including SOX2, KLF4, C-MYC; (c) downregulation of miRNA let-7b known to inhibit reprogramming; and (iv) increased efficiency of reprogramming to iPSCs in the presence of reprogramming factors. Together, our results indicate a direct functional link between miR-145 and molecular pathways underlying reprogramming of somatic cells to iPSCs.
authors.affiliation: International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.|Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Barta
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Peskova
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Collin
authors.affiliation: Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Montaner
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
authors.forename: Irina
authors.initials: I
authors.lastname: Neganova
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
authors.forename: Lyle
authors.initials: L
authors.lastname: Armstrong
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
authors.forename: Majlinda
authors.initials: M
authors.lastname: Lako
mesh_terms: D001483:Base Sequence; D065150:Cellular Reprogramming / Q000235:genetics; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D015203:Reproducibility of Results
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; C541010:MIRN145 microRNA, human; D035683:MicroRNAs
keywords: Induced pluripotent stem cells; KLF4; Mesenchymal-to-epithelial transition; OCT4; Reprogramming; SOX2; c-MYC; miR-145; microRNA