Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment.

ABSTRACT: One million patients with congenital heart disease (CHD) live in the United States. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. Here, analysis of heart tissue from an infant with tetralogy of Fallot with pulmonary stenosis (ToF/PS) labeled with isotope-tagged thymidine demonstrated that cardiomyocyte cytokinesis failure is increased in this common form of CHD. We used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure is repression of the cytokinesis gene ECT2, downstream of β-adrenergic receptors (β-ARs). Inactivation of the β-AR genes and administration of the β-blocker propranolol increased cardiomyocyte divi

SUBMITTER: Liu H 

PROVIDER: S-EPMC8132604 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature