# Genetic tracing and topography of spontaneous and stimulated cardiac regeneration in mice

## TL;DR

Researchers developed a new genetic method to track heart cell regeneration in mice, revealing how heart cells divide and renew under different conditions.

## Contribution

The novel CycleTrack method enables permanent and reliable labeling of dividing cardiomyocytes in vivo.

## Key findings

- CycleTrack visualizes cardiomyocyte turnover in neonatal and adult mice under various conditions.
- The subendocardium is identified as a key site of mitotic activity in the heart.
- CycleTrack provides evidence of remuscularization after treatment with pro-regenerative microRNAs.

## Abstract

Despite recent efforts to stimulate endogenous cardiomyocyte proliferation for cardiac regeneration, the lack of reliable in vivo methods for monitoring cardiomyocyte replication has hindered our understanding of its mechanisms. Thymidine analogs, used to label proliferating cells, are unsuitable for long-term cardiac regeneration studies as their DNA incorporation elicits a damage response, leading to their elimination. Here we present CycleTrack, a genetic strategy based on the transcriptional activation of Cre recombinase from a temporally regulated cyclin B2 promoter segment, for permanent labeling of cardiomyocytes passing through the G2/M phase. Using CycleTrack, we visualized cardiomyocyte turnover in neonatal and adult mice under various conditions, including pregnancy, increased ventricular afterload, and myocardial infarction. CycleTrack also provided visual and quantitative evidence of ventricular remuscularization following treatment with pro-regenerative microRNAs. We identify the subendocardium as a key site of mitotic activity and provide a mode of cardiomyocyte division along their short axis. CycleTrack is a powerful tool to monitor cardiomyocyte renewal during regenerative interventions.

Secco et al. develop a genetic tracing method, CycleTrack, to monitor cardiac regeneration. CycleTrack visualizes cardiomyocyte turnover in neonatal and adult mice, after myocardial infarction, and upon stimulation with pro-regenerative microRNAs.