Cardiomyocyte Chirality Defects in Congenital Heart Disease
Abstract
Congenital heart disease is the most common birth defect and affects approximated 40,000 newborns per year in the United States. Because of surgical advances, mortality from congenital heart disease has declined significantly and the result has been an incredible increase in the number of surviving adults with significant congenital heart disease. A large proportion of congenital heart disease is caused by a defect in correct partitioning of the left and right compartments of the cardiac mesoderm. The result of this failure of laterality is a wide assortment of abnormal atrial, ventricular and arterial relationships. Aberration of early left right patterning is the underlying cause of heterotaxy. The focus of this grant is to use induced pluripotent stem cells to model and understand inherent cellular laterality. We have generated a genetic model of heterotaxy using a CRISPR interference system that targets the expression of a transcription factor, ZIC3, that has been implicated in inherited versions of heterotaxy. During this final period, we have utilized both genetically altered and patient derived lines to characterize the cellular phenotype of heterotaxy, specifically addressing defects in cell migration and movement. We report here successful generation of left sided iPSC derivatives in response to ZIC3 loss. To our knowledge, this is the first description of left-right asymmetry in iPSC and genetic manipulation affecting that axis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2019
- Accession Number
- AD1097809
Entities
People
- Barry Fine
Organizations
- Trustees of Columbia University in the City of New York