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

1 Citation (Scopus)

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

Fingerprint

Histone Code
Transcriptome
Regeneration
Genes
RNA-Binding Proteins
Wounds and Injuries
Immunologic Factors
Cardiac Myocytes
Chromatin
Myocardial Infarction
Parturition

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling. / Wang, Zhaoning; Cui, Miao; Shah, Akansha M.; Ye, Wenduo; Tan, Wei; Min, Yi Li; Botten, Giovanni A.; Shelton, John M.; Liu, Ning; Bassel-Duby, Rhonda S; Olson, Eric N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 37, 10.09.2019, p. 18455-18465.

Research output: Contribution to journalArticle

Wang, Zhaoning ; Cui, Miao ; Shah, Akansha M. ; Ye, Wenduo ; Tan, Wei ; Min, Yi Li ; Botten, Giovanni A. ; Shelton, John M. ; Liu, Ning ; Bassel-Duby, Rhonda S ; Olson, Eric N. / Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 37. pp. 18455-18465.
@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 Bassel-Duby, {Rhonda S} and Olson, {Eric N}",
year = "2019",
month = "9",
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",
number = "37",

}

TY - JOUR

T1 - Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling

AU - Wang, Zhaoning

AU - Cui, Miao

AU - Shah, Akansha M.

AU - Ye, Wenduo

AU - Tan, Wei

AU - Min, Yi Li

AU - Botten, Giovanni A.

AU - Shelton, John M.

AU - Liu, Ning

AU - Bassel-Duby, Rhonda S

AU - Olson, Eric N

PY - 2019/9/10

Y1 - 2019/9/10

N2 - 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.

AB - 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.

KW - Cardiogenic gene program

KW - Epigenome profiling

KW - Immune response

KW - Myocardial infarction

KW - Transcriptome profiling

UR - http://www.scopus.com/inward/record.url?scp=85072056236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072056236&partnerID=8YFLogxK

U2 - 10.1073/pnas.1905824116

DO - 10.1073/pnas.1905824116

M3 - Article

C2 - 31451669

AN - SCOPUS:85072056236

VL - 116

SP - 18455

EP - 18465

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 37

ER -