Due to a very limited regenerative capacity of adult cardiomyocytes, a loss of cardiomyocytes caused by heart disease is not restored by endogenous mechanisms. We aimed to generate the basis for detecting cell cycle activity in real time, in order to understand the control of cell dynamics in cardiomyocytes. Our approach includes the generation of Fluorescence ubiquitination dependent cell cycle indicator (FUCCI) in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) based on engineering of endogenous proteins, which are distinctively expressed along the cell cycle. This system has been used in vivo and in vitro however models for human iPSC-derived cardiomyocyte cell cycle are scarce. Our approach consists of a stabilized Chromatin licensing and DNA replication factor 1 (CDT1) fused to mCherry as reporter marking the G1 phase. For G2 phase detection, Geminin, a DNA replication inhibitor, fused to TurboGFP is used as a marker. Ubiquitination and degradation of CDT1 or GEMININ throughout the cell cycle therefore allows identifying bona fide cell cycle progression as well as G1/S and G2/M checkpoints. We engineered previous FUCCI constructs to drive its expression under the ubiquitous CAG promoter. As a proof of concept, cell cycle was arrested in specific phases by using Thymidine (THY, arresting G1/S phase boundary) and Nocodazole (NOC, arresting G2 phase) in HEK293 T cells and quantified by live imaging using a CQ1 confocal imaging cytometer. Upon the treatment with THY, an enrichment of mCherry and TurboGFP reporter compared to the control group was observed (THY group n=6, control group n=3). Furthermore, the NOC treatment showed the enrichment of TurboGFP reporter compared to the control group (NOC group n=6, control group n=3). This result validated cell cycle phase detection with our FUCCI construct. To translate this system into hiPSC-CM, we took two approaches: (1.) integrated the FUCCI construct into a lentiviral plasmid and (2.) cloned it into a template vector suitable for CRISPR/Cas9 homology directed repair mediating integration in the AAVS1 safe harbor locus on human chromosome 19. The lentivirus approach was used to transduce hiPSC-CM, which expressed a Alpha-actinin-2 (ACTN2)-reporter fusion protein to detect transduced cardiomyocytes. Preliminary data suggests that five days after transduction, the majority of hiPSC-CM were in either G0 (colorless) or G1 (mCherry) phase as expected. To check the continuous changes in the cell cycle, THY and NOC were used consecutively to synchronize cell cycle activity. Control group (n=2), G1/S boundary arrested (THY) group (n=2), and G2 arrested group (THY and NOC, n=2) showed that hiPSC-CM only stayed in either G0 or G1 phase regardless of the presence of cell cycle arrest agents. In conclusion, we demonstrated FUCCI will enable to visualize endogenous cell cycle progression in real time in hiPSC-CM as a useful tool for the basic science community in regenerative cardiology. Currently, a double transgenic hiPSC-CM, which contains FUCCI and CRISPR/Cas9 activator is being established for studying transcriptional control of cell dynamics.