@article{f087542b2c0c409c89bcd94b147be17a,
title = "Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling",
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.",
keywords = "Cardiogenic gene program, Epigenome profiling, Immune response, Myocardial infarction, Transcriptome profiling",
author = "Zhaoning Wang and Miao Cui and Shah, {Akansha M.} and Wenduo Ye and Wei Tan and Min, {Yi Li} and Botten, {Giovanni A.} and Shelton, {John M.} and Ning Liu and Rhonda Bassel-Duby and Olson, {Eric N.}",
note = "Funding Information: ACKNOWLEDGMENTS. We dedicate this work to the memory of Wenduo Ye, an exceptional colleague and caring friend who generated data for this study. We thank Jose Cabrera for graphics, John McAnally for performing microinjection for the transgenic enhancer assay, Jian Xu and Xin Liu from the Sequencing Core Facility (Children{\textquoteright}s Research Institute at University of Texas Southwestern Medical Center) for performing the Illumina sequencing, and the Molecular Histopathology Core (University of Texas Southwestern Medical Center) under the direction of James Richardson for help with histology. We thank Hisayuki Hashimoto, Catherine Makarewich, and other members of the E.N.O. laboratory for helpful discussions. We are grateful for the support, advice, and assistance from Beibei Chen, Min S. Kim, and Venkat Malladi from the Bioinformatics Core Facility (University of Texas Southwestern Medical Center). We thank the ENCODE Consortium and the ENCODE production laboratories for generating the datasets used in this study. This work was supported by grants from the NIH (AR-067294, HL-130253, HL-138426, and HD-087351), the Fondation Leducq Transatlantic Networks of Excellence in Cardiovascular Research, and the Robert A. Welch Foundation (Grant 1-0025 to E.N.O.). Z.W. was supported by a predoctoral fellowship from the American Heart Association and the Harry S. Moss Heart Trust (19PRE34380436). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = sep,
day = "10",
doi = "10.1073/pnas.1905824116",
language = "English (US)",
volume = "116",
pages = "18455--18465",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "37",
}