Fig. 2.

Working model of injury-induced cardiomyocyte proliferation. Injury signals trigger the cell-cycle re-entry of CMs, leading to the formation of mononuclear, polynuclear, or polyploidy CMs. De-differentiation signals together with extracellular matrix (ECM) re-organization then regulate the generation of putative de-differentiated CMs, which have evident changes in mitochondrial morphology, disassembled sarcomeres, and reduced cell adhesion. Finally, reprogramming signals and mitogens drive the formation of putative progenitors and cell division