AI Article Synopsis
- This study investigates how well induced pluripotent stem cells (iPSCs) can model developmental cardiac defects by comparing gene expression in mouse models with heart issues and healthy embryonic tissues.
- Transcriptional analysis showed that iPSC-derived cells aligned about 50% with the gene expression patterns found in actual embryos, revealing key metabolic changes related to heart development.
- The findings suggest that iPSCs are a valuable model for studying the early stages of congenital heart defects, highlighting their potential for research in cardiac disease pathways.
Article Abstract
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=3.95×10(-12)) and down-regulation of fatty acid metabolism (p-value=6.71×10(-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.
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| http://dx.doi.org/10.1016/j.yjmcc.2015.08.021 | DOI Listing |
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