| First Author | Campbell KA | Year | 2015 |
| Journal | J Mol Cell Cardiol | Volume | 87 |
| Pages | 228-36 | PubMed ID | 26344701 |
| Mgi Jnum | J:250722 | Mgi Id | MGI:6101829 |
| Doi | 10.1016/j.yjmcc.2015.08.021 | Citation | Campbell KA, et al. (2015) Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis. J Mol Cell Cardiol 87:228-36 |
| abstractText | BACKGROUND: Through genome-wide transcriptional comparisons, this study interrogates the capacity of in vitro differentiation of induced pluripotent stem cells (iPSCs) to accurately model pathogenic signatures of developmental cardiac defects. METHODS AND RESULTS: Herein, we studied the molecular etiology of cardiac defects in Nos3(-/-) mice via transcriptional analysis of stage-matched embryonic tissues and iPSC-derived cells. In vitro comparisons of differentiated cells were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3(-/-) transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic tissues and ex vivo iPSC-derived cells. In particular, up-regulation of glucose metabolism (p-value=3.95x10(-12)) and down-regulation of fatty acid metabolism (p-value=6.71x10(-12)) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived differentiated cells. CONCLUSIONS: The in vitro concordance of early Nos3(-/-) disease signatures supports the utility of iPSCs as a cellular model of developmental heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of congenital cardiac pathogenesis. |
