Supplementary Materials

Supplementary Material for:

Neuregulin stimulation of cardiomyocyte regeneration in mice and human myocardium reveals a therapeutic window

Brian D. Polizzotti, Balakrishnan Ganapathy, Stuart Walsh, Sangita Choudhury, Niyatie Ammanamanchi, David G. Bennett, Cristobal G. dos Remedios, Bernhard J. Haubner, Josef M. Penninger, Bernhard Kühn*

*Corresponding author. E-mail: bernhard.kuhn2{at}chp.edu

Published 1 April 2015, Sci. Transl. Med. 7, 281ra45 (2015)
DOI: 10.1126/scitranslmed.aaa5171

This PDF file includes:

  • Materials and Methods
  • Results
  • Fig. S1. Contribution of cardiomyocyte proliferation to regeneration.
  • Fig. S2. Cryoinjured hearts showed loss of sacromeric organization.
  • Fig. S3. Characterization of myocardial repair after cryoinjury.
  • Fig. S4. Transmural scar persists even after 7 months after cryoinjury.
  • Fig. S5. Visualization of scar and quantification of cardiac function by MRI from early administration group.
  • Fig. S6. Visualization of scar and quantification of cardiac function by MRI for late administration group.
  • Fig. S7. Time course of myocardial repair after cryoinjury from early rNRG1 administration group.
  • Fig. S8. Time course of myocardial repair after cryoinjury from late rNRG1 administration group.
  • Fig. S9. Failure to visualize transmural scars with late gadolinium enhancement due to low spatial resolution of cMRI in mice.
  • Fig. S10. Schematic representation illustrating the nongenetic labeling technique with CFSE.
  • Fig. S11. rNRG1-stimulated cardiomyocyte proliferation in infants is age-dependent (2-month-, 6-month-, 1.5- to 5-year-, and 10-year-old patients).
  • Reference (46)
  • Table S1 (Microsoft Excel format). List of all differentially expressed genes between the BSA and rNRG1 treatment groups relative to sham mice (P < 0.05).
  • Table S2. Clinical information of patients with heart disease analyzed for Fig. 6C (H3P activity over age).
  • Table S3. Clinical information for normal hearts analyzed for Fig. 6C (H3P activity over age).
  • Table S4. Clinical information of patients with heart disease analyzed for Fig. 7D (rNRG1 stimulation).
  • Table S5. Clinical information of patients with heart disease analyzed for Fig. 8G (CFSE assay).
  • Table S6. Comparison of tissue response after cryoinjury in mice and myocardial disease in human infants (myocardial dysfunction, scar formation, and decreased cardiomyocyte cycling).
  • Table S7. Antibody manufacturers and dilutions.
  • Table S8. Image acquisition hardware and settings.
  • Table S9. Quantification of numeric data.
  • Table S10. Human primers for quantitative RT-PCR for calculation of fold change in expression levels.
  • Table S11. Mouse primers for quantitative PCR for calculation of fold change in expression levels.

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Other Supplementary Material for this manuscript includes the following:

  • Fig.S3.data.pdf
  • Fig.S5.data.pdf
  • Fig.S6.data.pdf
  • Fig.S7.data.pdf
  • Fig.S8.data.pdf
  • Fig.S11.data.pdf
  • Table S1.GeneExpressionData.xlsx
  • Movie S1 (.mov format). BSA-treated mouse from early administration.
  • Movie S2 (.mov format). rNRG1-treated mouse from early administration.
  • Movie S3 (.mov format). BSA-treated mouse from late administration.
  • Movie S4 (.mov format). rNRG1-treated mouse from late administration.
  • Movie S5 (.mov format). 3D reconstructions show myocardial syncytium adjacent to the scar after early administration (64 dpi).

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[Download Fig. S3.data.pdf]

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[Download Fig. S11.data.pdf]