Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome

Nana Takenaka-Ninagawa, Yuka Kawabata, Shogo Watanabe, Kohzo Nagata, Shigeko Torihashi

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Article numbere104462
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 11 2014
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
metabolic syndrome
Stem cells
Rats
rats
Mesenchymal Stromal Cells
stromal cells
Adipocytes
induced pluripotent stem cells
Adipose Tissue
adipocytes
adipose tissue
Inbred Dahl Rats
Zucker Rats
Germ Layers
Adipogenesis
Lentivirus
Tissue
Teratoma
Embryonic Stem Cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome. / Takenaka-Ninagawa, Nana; Kawabata, Yuka; Watanabe, Shogo; Nagata, Kohzo; Torihashi, Shigeko.

In: PLoS One, Vol. 9, No. 8, e104462, 11.08.2014.

Research output: Contribution to journalArticle

Takenaka-Ninagawa, Nana ; Kawabata, Yuka ; Watanabe, Shogo ; Nagata, Kohzo ; Torihashi, Shigeko. / Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome. In: PLoS One. 2014 ; Vol. 9, No. 8.
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