Transcriptional profiling of regenerating embryonic mouse hearts

Abstract

The postnatal mammalian heart is considered a terminally differentiated organ unable to efficiently regenerate after injury. In contrast, we have recently shown a remarkable regenerative capacity of the prenatal heart using myocardial tissue mosaicism for mitochondrial dysfunction in mice. This model is based on inactivation of the X-linked gene encoding holocytochrome c synthase (Hccs) specifically in the developing heart. Loss of HCCS activity results in respiratory chain dysfunction, disturbed cardiomyocyte differentiation and reduced cell cycle activity. The Hccs gene is subjected to X chromosome inactivation, such that in females heterozygous for the heart conditional Hccs knockout approximately 50% of cardiac cells keep the defective X chromosome active and develop mitochondrial dysfunction while the other 50% remain healthy. During heart development the contribution of HCCS deficient cells to the cardiac tissue decreases from 50% at mid-gestation to 10% at birth. This regeneration of the prenatal heart is mediated by increased proliferation of the healthy cardiac cell population, which compensates for the defective cells allowing the formation of a fully functional heart by birth. Here we performed microarray RNA expression analyses on 13.5 dpc control and heterozygous Hccs knockout hearts to identify molecular mechanisms that drive embryonic heart regeneration. Array data have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE72054.

Keywords

• Heart development
• Cardiac regeneration
• Cardiomyocyte proliferation
• Mitochondrial dysfunction
• Cellular stress response