Reciprocal analyses in zebrafish and medaka reveal that harnessing the immune response promotes cardiac regeneration
- Max Planck Institute for Heart and Lung Research, Germany
Figures
Figure 1
Comparative transcriptomic analyses between zebrafish and medaka after cardiac injury.
(A) Experimental design. Untouched, sham-operated, and cryoinjured zebrafish and medaka ventricles were collected at 6 hr, 1 d (zebrafish only), 2 d, 3 d, and 5 d (zebrafish only)/6 d (medaka only) …
Figure 2 with 1 supplement
Heatmaps of differentially enriched GO terms from SLEA.
GO terms from SLEA analysis of cryoinjured vs. untouched hearts related to immune response (A), cell proliferation (B), angiogenesis (C) and other biological processes (D), were selected and …
Figure 2—figure supplement 1
Heatmaps of enriched GO terms from SLEA.
GO terms from SLEA analysis of sham-operated vs. untouched hearts related to immune response (A), cell proliferation (B), angiogenesis (C) and other biological processes (D), were selected and …
Figure 3 with 1 supplement
Immune cells dynamics in cryoinjured hearts.
(A) Zebrafish and medaka heart sections at 6 hpci, 2 dpci and 7 dpci were stained with isolectin-B4 (IB4) for macrophages, and Mpx antibody for neutrophils. Positive cells, both in the injured area …
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Figure 3—source data 1
Quantification of immune cells in cryoinjured hearts.
- https://doi.org/10.7554/eLife.25605.006
Figure 3—figure supplement 1
Mpx antibody specifically stains mpx:GFP-expressing cells.
Injured hearts from adult mpx:GFP zebrafish were collected at 7 dpci, and cryosections stained with GFP and Mpx antibodies to examine neutrophils. Dotted lines delineate the injured area; scale …
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Figure 3—figure supplement 1—source data 1
Quantification of Mpx+ and mpx:GFP+ cells in zebrafish hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.008
Figure 4 with 2 supplements
Delayed macrophage recruitment in zebrafish compromises neovascularization, CM proliferation and scar resolution.
Adult zebrafish were injected with PBS or clodronate liposomes 1 day before injury. Hearts were collected at 1 dpci (A), 7 dpci (B and C) and 1 mpci (E–G) to examine macrophages by mpeg1:EGFP …
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Figure 4—source data 1
Quantification of proliferating CMs in control and CL-exposed zebrafish hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.010
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Figure 4—source data 2
Quantification of scar areas in control and CL-exposed zebrafish hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.011
Figure 4—figure supplement 1
Delayed macrophage recruitment in zebrafish by Clodronate liposome pre-depletion.
Adult mpeg1.4:mCherry-F;mpx:GFP zebrafish were injected with PBS or clodronate liposomes 1 day before injury. Hearts were collected at 7 dpci, and cryosections stained with GFP antibody to examine …
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Figure 4—figure supplement 1—source data 1
Quantification of macrophage and neutrophil numbers in control and CL-exposed zebrafish hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.013
Figure 4—figure supplement 2
Delayed macrophage recruitment in zebrafish compromises scar resolution.
Adult zebrafish were injected with PBS or clodronate liposomes 1 day before injury. Hearts were collected at 1 mpci, and cryosections were stained with AFOG. Healthy muscle stained in orange, fibrin …
Figure 5
Neutrophil clearance is delayed after macrophage pre-depletion.
Adult zebrafish were injected with PBS or clodronate liposomes 1 day before injury. Hearts were collected at 6 hpci (A), 2 dpci (A), 7 dpci (A and B), and 1 mpci (C and D) to examine macrophages by …
Figure 6
Poly I:C injection in medaka promotes macrophage recruitment and neutrophil clearance following cardiac injury.
(A) Medaka heart sections at 7 dpci were stained with IB4 for macrophages and Mpx antibody for neutrophils. Positive cells, both in the injured area itself and within 100 μm of the injured area, …
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Figure 6—source data 1
Quantification of macrophage and neutrophil numbers in control and poly I:C-exposed medaka hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.017
Figure 7
Poly I:C injection in medaka promotes neovascularization in a macrophage-dependent manner following cardiac injury.
Adult fli::GFP;gata1::GFP medaka were injected with PBS (A–E) or poly I:C (F–J) immediately after injury, or with clodronate liposomes at 1 day before injury and poly I:C immediately after injury (K)…
Figure 8
Poly I:C injection in medaka promotes CM proliferation in a macrophage-dependent manner following cardiac injury.
Adult zfmlc2 5.1 k:DsRED2-nuc medaka were injected with PBS or poly I:C immediately after injury, or with clodronate liposomes at 1 day before injury and poly I:C immediately after injury. Hearts …
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Figure 8—source data 1
Quantification of proliferating CMs in medaka hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.020
Figure 9
Poly I:C injection in medaka promotes scar resolution following cardiac injury.
Adult fli::GFP;gata1::GFP medaka were injected with PBS or poly I:C immediately after injury. Hearts were collected at 1 mpci, and scar composition and resolution were examined by AFOG staining. (A) …
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Figure 9—source data 1
Quantification of scar areas in medaka hearts following cardiac injury.
- https://doi.org/10.7554/eLife.25605.022
Additional files
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Supplementary file 1
Normalized orthologous genes expression in zebrafish and medaka post cardiac injury.
- https://doi.org/10.7554/eLife.25605.023
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Supplementary file 2
List of biological processes revealed by Sample Level Enrichment Analysis.
- https://doi.org/10.7554/eLife.25605.024
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Supplementary file 3
Top canonical pathways and upstream regulators predicted by Ingenuity Pathway Analysis.
(Z-zebrafish, M-medaka, H-hours post injury, D-days post injury.)
- https://doi.org/10.7554/eLife.25605.025
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Supplementary file 4
List of canonical pathways and upstream regulators predicted by Ingenuity Pathway Analysis.
- https://doi.org/10.7554/eLife.25605.026
