The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration
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ABSTRACT:
PROVIDER: PRJNA1091566 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28435452_1.fastq.gz | Fastqsanger.gz | |||
| SRR28435452_2.fastq.gz | Fastqsanger.gz | |||
| SRR28435453_1.fastq.gz | Fastqsanger.gz | |||
| SRR28435453_2.fastq.gz | Fastqsanger.gz | |||
| SRR28435454_1.fastq.gz | Fastqsanger.gz |
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Project description: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.
2024-07-29 | GSE262351 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. 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.
2024-07-29 | GSE262248 | GEO
Project description:The innate immune system is triggered rapidly after injury and its spatiotemporal dynamics are critical for successful regeneration. MyD88 is a key component of the innate immune response; however, its role during regeneration remains unclear. Here we show that MyD88 controls not only the inflammatory but also the fibrotic response during zebrafish cardiac regeneration. Our data reveal a significant reduction in pro-inflammatory neutrophil and macrophage populations, as well as the expansion of a collagen-rich endocardial population in cryoinjured myd88-/- ventricles. Consistent with these findings, we observed increased myofibroblasts, fibrin abundance, and scarring in myd88-/- ventricles. Transcriptomic analyses of endocardial cells and immunostaining experiments reveal compromised PI3K/AKT pathway activation in the myd88-/- endocardium. Moreover, loss of MyD88 impairs cardiomyocyte proliferation and protrusive activity towards the injured area. Notably, endothelial-specific overexpression of myd88 reverses the neutrophil, fibrotic, and scarring phenotypes in cryoinjured myd88-/- ventricles. Mechanistically, we identify the endocardial-derived chemokine gene cxcl18b as a transcriptional target of the MyD88-signaling axis 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, thereby emphasizing the strong impact of the innate immune response during tissue regeneration.
2024-07-29 | GSE262247 | GEO
Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration
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Project description: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.
2024-07-29 | GSE262169 | GEO
Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst139)
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Project description:The innate immune regulator MyD88 dampens fibrosis during zebrafish heart regeneration (dst169)
| PRJNA1090898 | ENA
Project description:Innate mesenchymal TLR4/MyD88 signals promote spontaneous intestinal tumorigenesis
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Project description:Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition.
2018-10-05 | GSE82200 | GEO
Project description:MyD88 is an adaptor protein in Toll-like receptor and interleukin 1 receptor mediated signaling pathways that plays an essential role in activation of immune responses following pathogen recognition. We investigate that role in the zebrafish embryo model by using a zebrafish mutant line that contains a premature stop condon in the gene encoding MyD88, leading to a truncated protein that lacks domains important for its normal function. We infected these MyD88 mutants and wildtype individuals with Mycobacterium marinum to compare the resulting immune response by transcriptome profiling on total RNA isolated from single embryos. Autophagy regulator dram1 was identified as one of the MyD88-dependent genes. This RNAseq analysis was used to determine the effect of a truncation of the MyD88 protein on the innate immune response of zebrafish embryos during infection with Mycobacterium marinum. Myd88 mutant and wild type embryos were derived by incrossing homozygous myd88 mutant parents (allele hu3568, van der Vaart et al., 2013, Disease models & mechanisms 6, 841-854) or their wildtype siblings. RNA was isolated from pools of 20 embryos at 4 days post infection (4 dpi). The following treatment groups were used: homozygous mutants mock-injected with PBS/2%PVP 4 dpi, (2) wildtype siblings mock-injected with PBS/2%PVP 4dpi, (3) M. marinum-infected homozygous mutants 4dpi, (4) M. marinum-infected wildtype siblings 4dpi. Embryos were grown at 28.5M-bM-^@M-^S30M-BM-0C in egg water and manually dechorionated at 24 hours post fertilization (hpf). Subsequently, embryos were infected at 28 hpf by micro-injecting 200 colony forming units (CFU) of Mycobacterium marinum Mma20 bacteria into the caudal vein, or were mock-injected with buffer (PBS/2%PVP) as a control. After injections embryos were transferred into fresh egg water and incubated for 4 days at 28M-BM-0C. After the incubation period, single embryos were snap-frozen in liquid nitrogen and RNA was isolated for RNAseq analysis.
2014-06-01 | E-GEOD-49186 | biostudies-arrayexpress