Differences between Cellular and Molecular Profiles of Induced Pluripotent Stem Cells Generated from Mouse Embryonic Fibroblasts

Abstract

Induced pluripotent stem (iPS) cells are a new alternative for the development of patient-specific stem cells, and the aim of this study was to determine whether differences exist between the cellular and molecular profiles of iPS cells, generated using lentiviral vectors, compared to ES cells. The lentiviral infection efficiency differed according to the method of cell culture (adherent cells: 0.085%; suspended cells: 0.785%). Six iPS cell lines exhibited typical ES cell morphology and marker expression, but varied in their in vitro/in vivo differentiation ability. Global gene transcription analysis revealed that core pluripotency genes were expressed at lower levels in iPS cell lines compared to D3-ES cells (Pou5f1: x1.6~2.2-fold, Sox2: x2.58~10.0-fold, Eras: x1.08~2.54-fold, Dppa5a: x1.04~1.41-fold), while other genes showed higher expression in iPS cells (Lin28: x1.43~2.33-fold; Dnmt3b: x1.33~2.64-fold). This pattern was repeated in a survey of specific functional groups of genes (surface markers, cell death, JAK-STAT and P13K-AKT signaling pathways, endothelial, cardiovascular, and neurogenesis genes). Among the iPS cell lines examined, only two showed similar characteristics to ES cells. These results demonstrated that, in addition to cellular characterization, the numerical evaluation of gene expression using DNA microarrays might help to identify the stem cell stability and pluripotency of iPS cells.