Insights into Cardiomyocyte Regeneration from Screening and Transcriptomics Approaches

Area of Science:

• Cardiovascular Biology
• Regenerative Medicine
• Genomics

Background:

• Human adult cardiomyocytes (CMs) possess limited regenerative capacity, hindering recovery from cardiac injury like myocardial infarction.
• Despite low baseline turnover, CMs can re-enter the cell cycle post-myocardial infarction, indicating potential for endogenous repair.
• Existing research focuses on identifying factors that promote CM rejuvenation and proliferation from existing cells.

Purpose of the Study:

• To compare high-throughput screening strategies for identifying novel cardiomyocyte proliferation targets.
• To summarize the advantages and disadvantages of various screening models for cardiac regeneration research.
• To provide a framework for advancing cardiac regeneration by integrating screening findings with CM heterogeneity insights.

Main Methods:

• Review and comparison of high-throughput screening strategies (small molecules, microRNAs, pathway interventions).
• Analysis of omics-based approaches like single-nucleus RNA sequencing and spatial transcriptomics for understanding cardiac cellular heterogeneity.
• Evaluation of diverse screening models: zebrafish embryos, rodent CMs, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and cardiac organoids.

Main Results:

• High-throughput screening has identified potential pro-proliferative targets for CMs.
• Omics approaches reveal insights into why only a subset of CMs re-enter the cell cycle.
• Integration of multiple screening systems is crucial for uncovering novel regenerative mechanisms.

Conclusions:

• Further research is needed to discover safe and translatable targets for functional CM expansion in clinical settings.
• Integrating high-throughput screening data with CM heterogeneity knowledge advances cardiac regeneration research.
• This review offers a comprehensive framework to guide future therapeutic development for cardiac repair.