|
| Status |
Public on Jul 15, 2019 |
| Title |
Epigenome profiling of neonatal heart regeneration |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Background: 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 non-regenerative mouse hearts over a 7-day time period following myocardial infarction.
Methods: RNA-Seq, H3K27ac ChIP-Seq and H3K27me3 ChIP-Seq were performed on ventricular samples from regenerative P1 or non-regenerative P8 mouse hearts at +1.5d, +3d and +7d after MI or Sham surgery to assemble the transcriptome, active chromatin and repressed chromatin landscapes during neonatal heart regeneration. Dynamic enhancer landscapes from mouse hearts during cardiac development were analyzed using data from ENCODE. Effects on cardiomyocyte proliferation and cardiac function from selected factors identified in this study were tested using BrdU/EdU pulse-labeling or mouse models coupled with immunohistochemistry and echocardiography.
Results: 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 an embryonic cardiogenic gene program that remains 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.
Conclusions: Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that might be modulated to promote heart regeneration.
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| Overall design |
We performed myocardial infarction (MI) or sham surgeries to mouse hearts at postnatal day 1 or day 8. At 1.5d, 3d or 7d post P1 and P8 surgery, ventricle samples below the surgery plane were collected in duplicate for H3K27ac and H3K27me3 ChIP-Seq
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| Contributor(s) |
Wang Z, Cui M, Tan W, Ye W, Botten GA, Olson EN |
| Citation(s) |
31451669, 33296652 |
| Submission date |
Dec 14, 2018 |
| Last update date |
Jan 04, 2021 |
| Contact name |
Zhaoning Wang |
| E-mail(s) |
zhw063@health.ucsd.edu
|
| Organization name |
UC San Diego
|
| Department |
Cellular and Molecular Medicine
|
| Lab |
Bing Ren Lab
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (72)
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| This SubSeries is part of SuperSeries: |
| GSE123868 |
Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling |
|
| Relations |
| BioProject |
PRJNA510092 |
| SRA |
SRP173467 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123867_P1_1.5MI_H3K27me3.fc.signal.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE123867_P1_1.5Sham_H3K27me3.fc.signal.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE123867_P1_3MI_H3K27me3.fc.signal.bw |
998.7 Mb |
(ftp)(http) |
BW |
| GSE123867_P1_3Sham_H3K27me3.fc.signal.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE123867_P1_7MI_H3K27me3.fc.signal.bw |
1.1 Gb |
(ftp)(http) |
BW |
| GSE123867_P1_7Sham_H3K27me3.fc.signal.bw |
1019.0 Mb |
(ftp)(http) |
BW |
| GSE123867_P8_1.5MI_H3K27me3.fc.signal.bw |
703.6 Mb |
(ftp)(http) |
BW |
| GSE123867_P8_1.5Sham_H3K27me3.fc.signal.bw |
698.7 Mb |
(ftp)(http) |
BW |
| GSE123867_P8_3MI_H3K27me3.fc.signal.bw |
1.2 Gb |
(ftp)(http) |
BW |
| GSE123867_P8_3Sham_H3K27me3.fc.signal.bw |
1.2 Gb |
(ftp)(http) |
BW |
| GSE123867_P8_7MI_H3K27me3.fc.signal.bw |
399.4 Mb |
(ftp)(http) |
BW |
| GSE123867_P8_7Sham_H3K27me3.fc.signal.bw |
632.8 Mb |
(ftp)(http) |
BW |
| GSE123867_RAW.tar |
9.7 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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