title: Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome.
abstract: We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of metabolic syndrome (MetS). Although the phenotype of DS/obese rats is similar to that of humans with MetS, the pathophysiological and metabolic characteristics in each cell type remain to be clarified. Hence, the establishment of induced pluripotent stem cells (iPSCs) derived from MetS rats is essential for investigations of MetS in vitro. Reports of rat iPSCs (riPSCs), however, are few because of the difficulty of comparing to other rodents such as mouse. Recently, the advantage of using mesenchymal stromal cells (MSCs) as a cell source for generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr+/Lepr+ (DS/lean) rats using lentivirus vectors with only three factors Oct4, Klf4, and Sox2 without c-Myc. The morphology, gene expression profiles, and protein expression of established colonies showed embryonic stem cell (ESCs)-like properties, and the differentiation potential into cells from all three germ layers both in vitro and in vivo (teratomas). Both riPSCs became adipocytes after induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR analysis also revealed that both riPSCs and the adipose tissue from DS/obese and DS/lean rats possess similar expression patterns of adipocyte differentiation-related genes. We succeeded in generating riPSCs effectively from MSCs of both DS/obese and DS/lean rats. These riPSCs may well serve as highly effective tools for the investigation of MetS pathophysiology in vitro.
authors.affiliation: Department of Rehabilitation Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Takenaka-Ninagawa
authors.affiliation: Department of Rehabilitation Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kawabata
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
authors.affiliation: Department of Rehabilitation Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Torihashi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D000090062:Kruppel-Like Factor 4; D059630:Mesenchymal Stem Cells / Q000166:cytology; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D051381:Rats
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4
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