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| Status |
Public on Jul 29, 2024 |
| Title |
The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The innate immune response is triggered rapidly after injury and its spatiotemporal dynamics are critical for regeneration, but many questions remain about its exact role. Here we show that MyD88, a key component of the innate immune response, controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. We find in cryoinjured myd88-/- ventricles a significant reduction in neutrophil and macrophage numbers as well as the expansion of a collagen-rich endocardial population. Further analyses reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium and increased myofibroblasts and scarring. Notably, endothelial-specific overexpression of myd88 reverses these neutrophil, fibrotic, and scarring phenotypes. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a target of the MyD88-signaling pathway, and using loss- and gain-of-function tools show that it controls neutrophil recruitment. Altogether, these findings shed light on the pivotal role of MyD88 in modulating inflammation and fibrosis during tissue regeneration.
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| Overall design |
Aim: Investigation of the MyD88 signaling in endocardial cells during zebrafish cardiac regeneration. Methods: Endocardial cells sorted from the ET(krt4:EGFP)sqet33-1A line at 96 hours post cryoinjury (hpci). Conditions: 3 myd88+/+ and 3 myd88-/- samples
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| Contributor(s) |
Goumenaki P, Guenther S, Khrievono K, Looso M, Marín-Juez R, Stainier DY |
| Citation(s) |
39271818 |
| |
| Submission date |
Mar 25, 2024 |
| Last update date |
Oct 09, 2024 |
| Contact name |
Noah Knoppik |
| Organization name |
Max-Planck-Institute for Heart and Lung Research
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| Department |
Bioinformatics
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| Street address |
Ludwigstrasse 43
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| City |
Bad Nauheim |
| ZIP/Postal code |
61231 |
| Country |
Germany |
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| Platforms (1) |
| GPL21741 |
Illumina HiSeq 4000 (Danio rerio) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1091566 |
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