Chi-Chung Wu (University of Heidelberg)

Regulatory mechanisms of chamber-specific cardiomyocyte polyploidization

Host: Felix Gunawan

Cardiomyocyte (CM) polyploidization (i.e., multiplication of the genome) is prevalent across mammals, including humans. Shortly after birth, mammalian CMs lose the ability to complete cell division and become polyploid, which is associated with their maturation and the loss of regenerative capacity of the heart. While the kinetics of ventricular CM polyploidization has been quite well characterized in several species, the spatiotemporal control and the underlying molecular mechanisms, in particular intercellular and cell-extracellular matrix interactions, remain poorly understood. We found that the degree of CM polyploidization differs significantly across heart chambers in mice; polyploid CMs are most abundant in the ventricle followed by the left atrium while the majority of right atrial CMs is mononuclear diploid. Transcriptomic analyzes revealed interesting differences in the composition of non-myocytes (e.g., immune cells and endothelium) as well as the extracellular matrix between the left and the right atria in the postnatal mouse heart. Using a combination of in vitro and in vivo models, we are currently investigating various aspects of cell-intrinsic and extrinsic regulatory mechanisms of postnatal CM polyploidization.

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