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Keywords {🔍}

macrophages, fig, pubmed, collagen, heart, supplementary, zebrafish, article, cas, scar, adult, google, scholar, hearts, cell, expression, cells, regeneration, data, injury, mouse, genes, day, dpi, central, macrophage, response, gfp, cardiac, cola, postmi, performed, nature, formation, mice, deposition, regenerative, transfer, gene, analysis, adoptive, monocytes, neonatal, revealed, cryoinjury, isolated, protein, transplanted, repair, tissue,

Topics {✒️}

nature portfolio biomedical services unit mrc/bbsrc/epsrc grant mr/k015777x/1 privacy policy pan-leukocytic marker l-plastin pro-regenerative/pro-resolution gene signatures advertising editing events tcf21-derived tissue-resident fibroblasts49 research ethics committee reaction solutions col4a3bpa/col4a1 crispr/cas9-targeted macrophages goodpasture antigen-binding protein macrophage-induced pro-fibrotic pathways crispr/cas9-mediated knock juan manuel gonzález-rosa reprints macrophage differentiation media col4a3bpa/col4a1-deficient macrophages revealed mf20-negative/dead muscle area turbo dna-free kit homology-independent intron targeting sequential z-stack series japan pro-fibrotic monocyte/macrophage response wimm single cell facility specific pathogen-free conditions intron-based protein trapping nuclei pulldown buffer npb buffer macrophage colony-stimulating factor col4a1+col4a3bpa crispr/cas9 macrophages mouse rna-seq datasets research design open biol macrophage-growing media nature nature 528 nature 454 nature 522 reporting summary distinct gene-regulatory programmes p1 rna-seq datasets cryo+col crispr/cas9 wild-type cd1 mice quantitative real-time pcr tissue-resident macrophage ontogeny color-coded probe pairs citrine-fused protein phenocopied gfptpz-collagen transgenic mice m-280 streptavidin-coated dynabeads

Questions {❓}

• The question remains as to why macrophages may act as collagen depositing cells during cardiac wound healing and fibrosis?

Schema {🗺️}

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         headline:Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair
         description:Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFPtpz-collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. Our 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. Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.
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      headline:Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair
      description:Canonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFPtpz-collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. Our 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. Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.
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