|
| Status |
Public on Sep 16, 2021 |
| Title |
Prrx1b restricts fibrosis and promotes Nrg1-dependent cardiomyocyte proliferation during zebrafish heart regeneration |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Fibroblasts are activated to repair the heart following injury. Fibroblast
activation in the mammalian heart leads to a permanent fibrotic scar
that impairs cardiac function. In other organisms, such as zebrafish,
cardiac injury is followed by transient fibrosis and scar-free
regeneration. The mechanisms that drive scarring versus scar-free
regeneration are not well understood. Here, we show that the
homeobox-containing transcription factor Prrx1b is required for
scar-free regeneration of the zebrafish heart as the loss of Prrx1b
results in excessive fibrosis and impaired cardiomyocyte proliferation.
Through lineage tracing and single-cell RNA sequencing we find that
Prrx1b is activated in epicardial-derived cells where it restricts TGFβ
ligand expression and collagen production. Furthermore, through
combined in vitro experiments in human fetal epicardial-derived
cells and in vivo rescue experiments in zebrafish, we conclude that
Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte
proliferation. Collectively, these results indicate that Prrx1 is a key
transcription factor that balances fibrosis and regeneration in the
injured zebrafish heart.
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| |
|
| Overall design |
Tg(tcf21:mCherry) positive cells (n=1438) were collected from cryoinjured hearts of wild-type (n = 20) and prrx1b-/- (n=20) ventricles. All cells were sent for single cell RNA sequencing.
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| |
|
| Contributor(s) |
de Bakker DE, Dronkers E, Bouwman M, Vink A, Goumans MJ, Smits A, Bakkers J |
| Citation(s) |
34486669 |
| |
| Submission date |
Jun 24, 2020 |
| Last update date |
Oct 27, 2021 |
| Contact name |
Dennis de de Bakker |
| E-mail(s) |
dennisdebakker@hotmail.com
|
| Phone |
+4915238951188
|
| Organization name |
FLI
|
| Street address |
Beutenbergstraße 11
|
| City |
Jena |
| ZIP/Postal code |
07745 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL20828 |
Illumina NextSeq 500 (Danio rerio) |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA641676 |
| SRA |
SRP268691 |
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