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| Status |
Public on Nov 04, 2020 |
| Title |
β-catenin drives distinct transcriptional networks in proliferative and non-proliferative cardiomyocytes |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. In contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms are not fully understood. Wnt/β-catenin signaling has been suggested as a key cardio-regenerative pathway. Here, we show that Wnt/β-catenin signaling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. In contrast, Wnt/β-catenin signaling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling of neonatal mouse and hPSC-CM revealed a core Wnt/β-catenin-dependent transcriptional network governing cardiomyocyte proliferation. In contrast, β-catenin failed to re-engage this proliferative gene network in the adult heart, which instead reverted to a neonatal-like glycolytic program. These findings suggest that Wnt/β-catenin drives distinct transcriptional networks in regenerative and non-regenerative cardiomyocytes, which may contribute towards the inability of the adult heart to regenerate following injury.
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| Overall design |
2D cardiac cells were treated with either 0.05% DMSO or 5 µM CHIR99021 for 24 hours and then sorted by FACS into cardiomyocyte (CD90-) and non-cardiomyocyte (CD90+) cell populations. Isolated cardiomycoytes from myocardial infarcted mice with AAV6 intramyocardial injections
2D cardiac cells were treated for 24 hours with 5 µm CHIR. hPSC-CMs were fixed for 10 minutes at room temperature with 1% paraformaldehyde (PFA). Cross-linking was stopped by addition 0.125M glycine for 5 minutes and ChIP-seq was performed
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| Contributor(s) |
Quaife-Ryan GA, Porrello ER, Hudson JE |
| Citation(s) |
33144401 |
| |
| Submission date |
May 13, 2020 |
| Last update date |
Nov 04, 2020 |
| Contact name |
James Hudson |
| E-mail(s) |
James.Hudson@QIMRBerghofer.edu.au
|
| Organization name |
QIMR Berghofer Medical Research Institute
|
| Lab |
Cardiac Bioengineering Laboratory
|
| Street address |
300 Herston Rd
|
| City |
Brisbane |
| State/province |
QLD |
| ZIP/Postal code |
4006 |
| Country |
Australia |
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| Platforms (3) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (28)
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| Relations |
| BioProject |
PRJNA632627 |
| SRA |
SRP261505 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE150521_20200506_CHIRvsDMSO_CD90+.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE150521_20200506_CHIRvsDMSO_CPM.txt.gz |
1.5 Mb |
(ftp)(http) |
TXT |
| GSE150521_20200506_CHIRvsDMSO_Count_matrix.txt.gz |
545.5 Kb |
(ftp)(http) |
TXT |
| GSE150521_20200506_CHIRvsDMSO_Myo.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE150521_20200506_MIP56.BCATvsGFP.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE150521_20200506_MIP56.BCATvsGFP_CPM.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE150521_20200506_MIP56.BCATvsGFP_Countmatrix.txt.gz |
391.8 Kb |
(ftp)(http) |
TXT |
| GSE150521_H3K27ac_consensus.bed.txt.gz |
522.0 Kb |
(ftp)(http) |
TXT |
| GSE150521_H3K4me3_consensus.bed.txt.gz |
289.4 Kb |
(ftp)(http) |
TXT |
| GSE150521_TCF7L2_consensus.bed.txt.gz |
114.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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