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  • 标题:Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling
  • 本地全文:下载
  • 作者:Zhaoning Wang ; Zhaoning Wang ; Miao Cui
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:37
  • 页码:18455-18465
  • DOI:10.1073/pnas.1905824116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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..
  • 关键词:transcriptome profiling ; epigenome profiling ; immune response ; myocardial infarction ; cardiogenic gene program
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