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Updated: Apr 4, 2026
Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis
Katherine A Campbell1, Xing Li2, Sherri M Biendarra3
1Department of Molecular Pharmacology and Experimental Therapeutics, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA; Center for Regenerative Medicine, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA; Division of General Internal Medicine, 200 First Street SW, Mayo Clinic, Rochester, MN 55905, USA.
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.
