RNA-sequencing from wild-type (WT) or Tie2-Ino80 knockout (KO) mouse embryo hearts

Purpose: Endothelial cell-specific knockout of the INO80 chromatin-remodeling complex in developing mouse embryos results in defective coronary angiogenesis. Transcriptome analysis on whole hearts was performed to understand how Ino80 regulates the genome to influence angiogenesis. Methods: mRNA was extracted from whole hearts after surgical removal from embryonic day 13.5 mice, either WT or Tie2-Ino80 KO, and prepped for Illumina sequencing using the NEBNext Ultra RNA Library Prep kit. Results: Deletion of Ino80 in the two major coronary progenetiors results in intermediate non-compaction phenotypes and an increase in E2F-mediated gene expression and cellular proliferation. Conclusions: Ino80 normally functions to suppress E2F-mediated proliferation in cardiac endothelial cells in order to promote productive angiogenesis and prevent underdevelopment of the myocardium heart muscle. Loss of this critical chromatin-remodeling function results in human disease phenotypes. mRNA profiles from embryonic day E13.5 mice were generated from WT or Tie2-Ino80-KO whole hearts using deep sequencing with three biological replicates for each. An average of 33.9M and 53.5M reads per replicate were included in the final analysis for the WT and KO samples, respectively.