Induced Pluripotent Stem Cells With Six Reprogramming Factors From Prairie Vole, Which Is an Animal Model for Social Behaviors

Cell Transplant. 2016;25(5):783-96. doi: 10.3727/096368916X690502. Epub 2016 Jan 15.

Abstract

Prairie voles show strong pair bonding with their mating partners, and they demonstrate parental behavior toward their infants, indicating that the prairie vole is a unique animal model for analysis of molecular mechanisms of social behavior. Until a recent study, the signaling pathway of oxytocin was thought to be critical for the social behavior of prairie voles, but neuron-specific functional research may be necessary to identify the molecular mechanisms of social behavior. Prairie vole pluripotent stem cells of high quality are essential to elucidate the molecular mechanisms of social behaviors. Generation of high-quality induced pluripotent stem cells (iPSCs) would help to establish a genetically modified prairie vole, including knockout and knock-in models, based on the pluripotency of iPSCs. Thus, we attempted to establish high-quality prairie vole-derived iPSCs (pv-iPSCs) in this study. We constructed a polycistronic reprogramming vector, which included six reprograming factors (Oct3/4, Sox2, Klf4, c-myc, Lin28, and Nanog). Furthermore, we evaluated the effect of six reprogramming factors, which included Oct3/4 with the transactivation domain (TAD) of MyoD. Implantation of the pv-iPSCs into immunodeficient mice caused a teratoma with three germ layers. Furthermore, the established pv-iPSCs tested positive for stem cell markers, including alkaline phosphatase activity (ALP), stage-specific embryonic antigen (SSEA)-1, and dependence on leukemia inhibitory factor (LIF). Our data indicate that our newly established pv-iPSCs may be a useful tool for genetic analysis of social behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Arvicolinae
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cellular Reprogramming*
  • Disease Models, Animal
  • Induced Pluripotent Stem Cells / cytology*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / metabolism
  • Leukemia Inhibitory Factor / metabolism
  • Lewis X Antigen / metabolism
  • Mice
  • Mice, SCID
  • Models, Animal
  • Nanog Homeobox Protein / metabolism
  • Octamer Transcription Factor-3 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • SOXB1 Transcription Factors / metabolism
  • Social Behavior*

Substances

  • Biomarkers
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Leukemia Inhibitory Factor
  • Lewis X Antigen
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Alkaline Phosphatase