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

Overview

abstract

  • 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.

authors

  • Cao, Jingli
  • Navis, Adam
  • Cox, Ben D
  • Dickson, Amy L
  • Gemberling, Matthew
  • Karra, Ravi
  • Bagnat, Michel
  • Poss, Kenneth D

publication date

  • December 10, 2015

Research

keywords

  • Caveolin 1
  • Heart
  • Pericardium
  • Regeneration

Identity

PubMed Central ID

  • PMC4725347

Scopus Document Identifier

  • 84954512505

Digital Object Identifier (DOI)

  • 10.1242/dev.130534

PubMed ID

  • 26657776

Additional Document Info

volume

  • 143

issue

  • 2