Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling

Zhaoning Wang, Miao Cui, Akansha M. Shah, Wenduo Ye, Wei Tan, Yi Li Min, Giovanni A. Botten, John M. Shelton, Ning Liu, Rhonda S Bassel-Duby, Eric N Olson

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and nonregenerative mouse hearts over a 7-d time period following myocardial infarction injury. By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration, and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and a retained embryonic cardiogenic gene program that is active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that can be modulated to promote heart regeneration.

Original languageEnglish (US)
Pages (from-to)18455-18465
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number37
DOIs
StatePublished - Sep 10 2019

Keywords

  • Cardiogenic gene program
  • Epigenome profiling
  • Immune response
  • Myocardial infarction
  • Transcriptome profiling

ASJC Scopus subject areas

  • General

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