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| Status |
Public on Dec 18, 2019 |
| Title |
Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Canonical roles for macrophages in mediating the fibrotic response after a heart attack (myocardial infarction) include turnover of the extracellular matrix and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal through studying the functional kinetics of fibrosis during zebrafish heart regeneration and mouse heart repair that macrophages can directly contribute collagen to the forming scar. Unbiased transcriptomics revealed an up-regulation of collagen isoforms in both zebrafish and mouse macrophages following injury. Adoptive transfer of macrophages from collagen-tagged transgenic zebrafish and splenic monocyte-derived macrophages from adult mouse GFPtpz-collagen donors, enhanced scar formation and induced fibrosis, respectively, via cell autonomous production of collagen. In zebrafish, macrophage-specific targeting of collagen 4a binding protein and cognate collagen 4a1 followed by transfer led to significantly reduced scarring in cryo-injured hosts. These findings contrast with the current model of scarring whereby collagen deposition is exclusively attributed to myofibroblasts, and implicate macrophages as direct contributors to fibrosis during heart repair.
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| Overall design |
Whole nuclear transcriptome profiling of macrohages in response to 2 types of heart injury (ventricular resection and cryo-injury) at 3 different stages of regenerative process in the zebrafish heart.
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| Contributor(s) |
Simões FC, Kenyon A, Gavriouchkina D, Weinberger M, Masmanian E, Meyes S, Sauka-Spengler T, Riley PR |
| Citation(s) |
32001677 |
| |
| Submission date |
Jun 14, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Tatjana Sauka-Spengler |
| E-mail(s) |
tatjana.sauka-spengler@imm.ox.ac.uk
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| Organization name |
MRC Weatherall Institute of Molecular Medicine
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| Department |
University of Oxford
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| Lab |
Sauka-Spengler lab
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| Street address |
Radcliffe Department of Medicine
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| City |
Oxford |
| State/province |
Oxfordshire |
| ZIP/Postal code |
OX3 9DS |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL20828 |
Illumina NextSeq 500 (Danio rerio) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA390533 |
| SRA |
SRP109201 |
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