Clonal Tracing of Heart Regeneration
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Published on: March 17, 2020
Kamal Kolluri1, Taline Nazarian1, Reza Ardehali1,2,3,4
1Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Insights
Adult heart cells (cardiomyocytes) have limited regeneration. This review explores lineage tracing methods, like mosaic analysis with double markers and rainbow reporters, to study cardiomyocyte proliferation after heart injury.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Developmental Biology
Background:
- Adult mammalian cardiomyocytes exhibit minimal turnover under homeostatic conditions.
- Myocardial injury leads to irreversible cardiomyocyte loss, resulting in scar formation and cardiac remodeling.
- Understanding cardiomyocyte proliferative capacity is crucial for developing cardiac repair strategies.
Purpose of the Study:
- To review in vivo methods for tracking cardiomyocyte fate and proliferation.
- To characterize the proliferative capacity of cardiomyocytes during development and after injury.
- To highlight the utility of lineage tracing models in studying cardiac regeneration.
Main Methods:
- Review of established lineage tracing techniques in transgenic mouse models.
- Focus on Mosaic Analysis with Double Markers (MADM) for clonal analysis.
- Discussion of the Rainbow reporter system for multicolor lineage tracing.
Main Results:
- Lineage tracing models provide long-term tracking of cell proliferation events.
- These models enable detailed analysis of cardiomyocyte behavior in response to physiological and pathological stimuli.
- Specific models like MADM and Rainbow offer distinct advantages for studying cell fate.
Conclusions:
- Lineage tracing is a powerful approach to investigate cardiomyocyte regeneration potential.
- The reviewed transgenic models are valuable tools for advancing cardiac research.
- Further application of these methods can elucidate mechanisms of cardiac repair and inform therapeutic development.
Abstract:
Cardiomyocytes in the adult mammalian heart have a low turnover during homeostasis. After myocardial injury, there is irreversible loss of cardiomyocytes, which results in subsequent scar formation and cardiac remodeling. In order to better understand and characterize the proliferative capacity of cardiomyocytes, in vivo methods have been developed to track their fate during normal development and after injury. Lineage tracing models are of particular interest due to their ability to record cell proliferation events over a long period of time, either during development or in response to a pathological event. This paper reviews two well-studied lineage-tracing, transgenic mouse models-mosaic analysis with double markers and rainbow reporter system.
