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| Status |
Public on Apr 16, 2020 |
| Title |
runx1 controls zebrafish heart regeneration by promoting scar deposition as well as inhibiting myocardial proliferation and survival |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Runx1 is a transcription factor that plays a key role in determining the proliferative and differential state of multiple cell types, during both development and adulthood. Here, we report how runx1 is specifically upregulated at the injury site during zebrafish heart regeneration, but unexpectedly, absence of runx1 results in enhanced regeneration. Using single cell sequencing, we found that the wild-type injury site consists of Runx1-positive endocardial cells and thrombocytes that express smooth muscle and collagen genes without differentiating into myofibroblasts. Both these populations are absent in runx1 mutants, resulting in a less collagenous and fibrinous scar. The reduction in fibrin in the mutant is further explained by reduced myofibroblast formation and by upregulation of components of the fibrin degradation pathway, including plasminogen receptor Annexin 2A as well as downregulation of plasminogen activator inhibitor serpine1 in myocardium and endocardium, resulting in increased levels of Plasminogen. In addition, this we also find enhanced myocardial proliferation as well as increased myocardial survival in the mutant. Our findings suggest that Runx1 controls the regenerative response of multiple cardiac cell-types and that targeting Runx1 is a novel therapeutic strategy to induce endogenous heart repair.
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| Overall design |
To determine the differences between wild type, wild type injured and wild type runx1 KO runx1+ endothelial cells in Zebrafish
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| Contributor(s) |
Koth J, Wang X, Killen AC, Stockdale WT, Potts H, Jefferson A, Bonkhofer F, Riley PR, Patient R, Göttgens B, Mommersteeg MT |
| Citation(s) |
32341028 |
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| Submission date |
Sep 30, 2019 |
| Last update date |
May 18, 2020 |
| Contact name |
Bertie Gottgens |
| Organization name |
University of Cambridge
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| Department |
Haematology
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| Street address |
Hills Road
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| City |
Cambridge |
| ZIP/Postal code |
CB2 0XY |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL18413 |
Illumina HiSeq 2500 (Danio rerio) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA575000 |
| SRA |
SRP223736 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE138181_RAW.tar |
31.1 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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