Journal
DEVELOPMENT
Volume 148, Issue 18, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.199740
Keywords
Cardiac; Live-imaging; Proliferation; Regeneration; Sarcomere; Zebrafish
Categories
Funding
- Hartstichting and Stichting Hartekind
- Hartstichting
- Stichting Hartekind (ERA-CVD PRO-HEART)
- Stichting Hartekind ( CVON OUTREACH)
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In this study, a cardiac slice culture system was developed to enable real-time imaging of native cardiomyocyte dynamics, allowing for the discovery of cellular mechanisms during heart regeneration. This system provides a new research method for studying cardiomyocyte proliferation and allows for interventions with drugs.
Zebrafish are excellent at regenerating their heart by reinitiating proliferation in pre-existing cardiomyocytes. Studying how zebrafish achieve this holds great potential in developing new strategies to boost mammalian heart regeneration. Nevertheless, the lack of appropriate live-imaging tools for the adult zebrafish heart has limited detailed studies into the dynamics underlying cardiomyocyte proliferation. Here, we address this by developing a system in which cardiac slices of the injured zebrafish heart are cultured ex vivo for several days while retaining key regenerative characteristics, including cardiomyocyte proliferation. In addition, we show that the cardiac slice culture system is compatible with live timelapse imaging and allows manipulation of regenerating cardiomyocytes with drugs that normally would have toxic effects that prevent their use. Finally, we use the cardiac slices to demonstrate that adult cardiomyocytes with fully assembled sarcomeres can partially disassemble their sarcomeres in a calpain- and proteasome-dependent manner to progress through nuclear division and cytokinesis. In conclusion, we have developed a cardiac slice culture system, which allows imaging of native cardiomyocyte dynamics in real time to discover cellular mechanisms during heart regeneration.
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