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

First Author  Wang Z Year  2019
Journal  Proc Natl Acad Sci U S A Volume  116
Issue  37 Pages  18455-18465
PubMed ID  31451669 Mgi Jnum  J:279371
Mgi Id  MGI:6360533 Doi  10.1073/pnas.1905824116
Citation  Wang Z, et al. (2019) Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling. Proc Natl Acad Sci U S A 116(37):18455-18465
abstractText  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.
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