Harnessing developmental cues for cardiomyocyte production

Abstract

Developmental research has attempted to untangle the exact signals that control heart growth and size, with knockout studies in mice identifying pivotal roles for Wnt and Hippo signaling during embryonic and fetal heart growth. Despite this improved understanding, no clinically relevant therapies are yet available to compensate for the loss of functional adult myocardium and the absence of mature cardiomyocyte renewal that underlies cardiomyopathies of multiple origins. It remains of great interest to understand which mechanisms are responsible for the decline in proliferation in adult hearts and to elucidate new strategies for the stimulation of cardiac regeneration. Multiple signaling pathways have been identified that regulate the proliferation of cardiomyocytes in the embryonic heart and appear to be upregulated in postnatal injured hearts. In this Review, we highlight the interaction of signaling pathways in heart development and discuss how this knowledge has been translated into current technologies for cardiomyocyte production.

In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease

“…Following this, the latest genomic findings and approaches that have been at the forefront of current CHD science over the last decade are discussed. Key signals that govern cardiac morphogenesis have been extensively examined in several informative reviews, which are recommended for further details, including publications [28][29][30][31][32][33][34][35]. Genes with harmful variants found in people with CHD are highlighted in bold during the report (Figure 4, [22,23,[36][37][38][39][40]).…”

“…The expression of key cardiac transcripts required for cardiomyocyte lineage commitment is reduced in experimental models by the deletion of genes encoding BMPs [50]. The expressions of genes such as GATA4, GATA6, NKX2-5, and TBX5 control sarcomere formation and contraction [28][29][30][31][32][33]51]. Ventricular cardiomyocyte specification is promoted by the expression of IRX4 in both the FHF and SHF of the cardiac crescent [52].…”