Regeneration potential of adult cardiac myocytes

Abstract

Although adult cardiac myocytes (CMs) have very little proliferative potential, fetal CMs divide robustly. The mechanisms underlying the post-mitotic state of CMs are poorly understood; however, recently Mahmoud et al. identified a homeodomain transcription factor, Meis1, which controls postnatal CM cell cycle.

Figure 1

Mechanisms that limit regenerative capacity of postnatal CMs. Three mechanisms have been identified to explain the limited cell cycle progression in adult CMs. 1) Pre-transcriptional heterochromatin-mediated gene silencing: positive cell cycle regulator genes are marked by silencing epigenetic marks (H3K9me3, HP1s) and packed into heterochromatin, resulting in permanent silencing. 2) miRNA regulation: miRNAs post-transcriptionally suppress gene clusters involved in CM regeneration. 3) Transcriptional activation: Meis1 activates transcription of negative cell cycle regulator genes.