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Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.

Publication ,  Journal Article
Cao, J; Navis, A; Cox, BD; Dickson, AL; Gemberling, M; Karra, R; Bagnat, M; Poss, KD
Published in: Development
January 15, 2016

In contrast to mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of cardiomyocytes spared from damage. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. Although it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. Here, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin 1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration.

Duke Scholars

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Published In

Development

DOI

EISSN

1477-9129

Publication Date

January 15, 2016

Volume

143

Issue

2

Start / End Page

232 / 243

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Regeneration
  • Pericardium
  • Myocytes, Cardiac
  • Heart
  • Caveolin 1
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Cao, J., Navis, A., Cox, B. D., Dickson, A. L., Gemberling, M., Karra, R., … Poss, K. D. (2016). Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration. Development, 143(2), 232–243. https://doi.org/10.1242/dev.130534
Cao, Jingli, Adam Navis, Ben D. Cox, Amy L. Dickson, Matthew Gemberling, Ravi Karra, Michel Bagnat, and Kenneth D. Poss. “Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.Development 143, no. 2 (January 15, 2016): 232–43. https://doi.org/10.1242/dev.130534.
Cao J, Navis A, Cox BD, Dickson AL, Gemberling M, Karra R, et al. Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration. Development. 2016 Jan 15;143(2):232–43.
Cao, Jingli, et al. “Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.Development, vol. 143, no. 2, Jan. 2016, pp. 232–43. Pubmed, doi:10.1242/dev.130534.
Cao J, Navis A, Cox BD, Dickson AL, Gemberling M, Karra R, Bagnat M, Poss KD. Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration. Development. 2016 Jan 15;143(2):232–243.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

January 15, 2016

Volume

143

Issue

2

Start / End Page

232 / 243

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Regeneration
  • Pericardium
  • Myocytes, Cardiac
  • Heart
  • Caveolin 1
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences