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| Status |
Public on Aug 18, 2020 |
| Title |
PRMT1-Mdm4-p53 pathway controls epicardial invasion and cell fate transition |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Epicardial cells are progenitors giving rise to the majority of cardiac fibroblasts, coronary smooth muscle cells, and pericytes during cardiac development, and critically modulating heart morphogenesis and coronary development. An integral phase of epicardial cell fate transition is epithelial-to-mesenchymal transition (EMT), which confers motility and facilitates cell fate transition. We identify a pathway involving protein arginine methyltransferase 1 (PRMT1) and its downstream p53 signaling that drives epicardial EMT and invasion. We show that PRMT1 determines the half-life of p53 through regulating alternative splicing of Mdm4, which is a key controller of p53 degradation. Loss of PRMT1 promotes the expression of Mdm4 short form, which inhibits p53 degradation. Accumulation of p53 subsequently enhances Slug degradation and blocks epicardial EMT. We further demonstrated that the PRMT1-Mdm4-p53 pathway drives epicardial cell fate transition into cardiac fibroblasts, coronary smooth muscle cells and pericytes in vivo, and modulates ventricular morphogenesis and coronary vessel formation. Together, our results establish critical functions of the PRMT1-Mdm4-p53 pathway in epicardial EMT, invasion and cell fate transition.
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| Overall design |
8 groups analyzed, 2 biological replicates per group. Total of 16 samples.
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| Contributor(s) |
Jackson-Weaver O, Qian J, Gou Y, Wu J, Shen H, Chen Y, Li M, Sucov H, Xu J |
| Citation(s) |
32521264 |
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| Submission date |
Nov 05, 2018 |
| Last update date |
Aug 18, 2020 |
| Contact name |
Olan Jackson-Weaver |
| E-mail(s) |
ojacksonweaver@gmail.com
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| Phone |
3238774119
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| Organization name |
Tulane University
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| Department |
Surgery
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| Street address |
1430 Tulane Ave, Department of Surgery
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| City |
New Orleans |
| State/province |
Louisiana |
| ZIP/Postal code |
70118 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA503912 |
| SRA |
SRP167901 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122200_OJ_p53mec1_GeneLevelQuantification.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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