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Zebrafish Heart Regeneration Occurs by Cardiomyocyte Dedifferentiation and Proliferation

Zebrafish Heart Regeneration Occurs by Cardiomyocyte Dedifferentiation and Proliferation. Yajun Lin (Jocelyn). Circulation Research August 4, 2006; 99 (3). Outline. Heart Disease – heart failure Heart Regeneration Green Fluorescent Protein

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Zebrafish Heart Regeneration Occurs by Cardiomyocyte Dedifferentiation and Proliferation

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  1. Zebrafish Heart Regeneration Occurs by Cardiomyocyte Dedifferentiation and Proliferation Yajun Lin (Jocelyn) Circulation Research August 4, 2006; 99 (3)

  2. Outline • Heart Disease – heart failure • Heart Regeneration • Green Fluorescent Protein • Mechanistic Insight of Zebrafish Heart Regeneration

  3. Heart Disease CDC, National Vital Statistics System and the U.S. Census Bureau.

  4. Heart Regeneration in Human Mercader et al.European Society of Cardiology (2013)

  5. Zebrafish Heart Regeneration Aumanetal.PLoSBiol.: 2007, 5(3);e53 PMID:17311471

  6. Mechanistic Insight of Zebrafish Heart Regeneration • Research done by Jopling et al. • Barcelona, Spain.

  7. Preparation • Transgenic zebrafish were generated in which 4-OHT-inducble Cre in under the control of the cardiomyocyte-specific cmlc2a promoter. • The reporter construct used the same cmlc2a promoter followed by a floxed stop cassette and enhanced green fluorescent protein. • Removal of the stop cassette by Cre allows the cmlc2a promoter within the transgene to drive the expression of GFP.

  8. GreenFluorescentProtein

  9. Regenerated cardiomyocytes are derived from differentiated cardiomyocytes. C Joplinget al.Nature464, 606-609 (2010) doi:10.1038/nature08899

  10. Differentiated cardiomyocytes re-enter the cell cycle. C Joplinget al.Nature464, 606-609 (2010) doi:10.1038/nature08899

  11. Cardiomyocytes dedifferentiate, resulting in the disassembly of sarcomeric structure and detachment. C Joplinget al.Nature464, 606-609 (2010) doi:10.1038/nature08899

  12. plk1 is necessary for cardiac regeneration. C Joplinget al.Nature464, 606-609 (2010) doi:10.1038/nature08899

  13. Conclusion • Zebrafishheartregenerationisdrivenprimarybypre-existingcardiomyocytes • Thevestmajorityofheartmusclecellarisefrimpre-existingcardiomyocytes • Pre-existingcardiomyocytesundergolimiteddedifferentiation. • Cardiomyocytesclosetothewoundstarttodisassembletheirsarcomericstructure,re-enteringthecellcycle. • Manysarcomericgenebeingdownregulatedafteramputation.

  14. References • Heidi J Auman, Hope Coleman, Heather E Riley, Felix Olale, Huai-Jen Tsai, Deborah YelonFunctional modulation of cardiac form through regionally confined cell shape changes.PLoS Biol.: 2007, 5(3);e53 PMID:17311471 • Laflamme, Michael A, and Charles E Murry. 2011. "Heart regeneration." Nature 473, no. 7347: 326-335. • The 2006 Holiday Lectures Series "Potent Biology: Stem Cells, Cloning, and Regeneration.” • Jopling, Chris, Eduard Sleep, Marina Raya, MercèMartí, Angel Raya, and Juan Carlos Izpisúa Belmonte. 2010. "Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation." Nature464, no. 7288: 606-609. • O. Shimomura, FH Johnson, and Y Saiga (1962). Extraction, Purification and Properties of Aequorin, a Bioluminescent Protein from the Luminous Hydromedusan, Aequorea. J. Cellular and Comparative Physiol. 59: 223-239 • Roger Heim, Andrew B. Cubitt & Roger Y. Tsien (1995) Improved Green Fluorescence. Nature. 373: 663-664.

  15. TheEnd

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