Abstract 14573: Cardiac Developmental Roadmap Predicts Cardiogenic Outcome of Pluripotent Stem Cells
Rationale: Cardiogenic development is a complex process giving rise to an integrated, multi-lineage cardiac tissue. Interrogation of individual genes has provided the backbone for cardiac developmental biology, yet stem cell-based cardiac regeneration requires an unbiased gene expression blueprint based on natural milestones to serve as a roadmap and ultimately focus efforts aiming to bioengineer functional cardiac tissue.
Objective: Establish a bioinformatic database of spatial-temporal structures staged according to embryonic cardiogenesis and validate a predictive tool to gauge cardiogenic outcomes from individual pluripotent stem cell lines.
Methods and results: Cardiac structures were surgically dissected from staged embryos and subjected to genome-wide expressome analysis. Unsupervised hierarchical cluster analysis demonstrated definitive separation of cardiac tissues to produce a sequential time-course of cardiogenic gene expression. A matrix for 72 genes revealed a dose-response of gene expression from pluripotent stem cells to adult heart muscle. Overlaying equivalent gene expression data sets derived from pluripotent stem cells lines differentiated in vitro at days 0, 5, and 11 allowed a comparative analysis and calibration to the roadmap. Comparing highly cardiogenic and poorly cardiogenic cell lines highlighted divergent pathways at day 5 of the pre-cardiac stage, predicting the compromised cardiac outcome and suggesting disruption of mechanisms necessary for functional cardiogenesis.
Conclusions: Bioinformatic analysis attuned to the embryonic developing heart provides a robust platform to probe coordinated cardiac specification and maturation. Herein, this genome-wide expressome roadmap allowed differential prognosis of the cardiogenic competency of independent reprogrammed cell lines, defining mechanisms of cardiogenesis sufficient to gauge bioengineered cardiac potential.
- © 2012 by American Heart Association, Inc.