Fig. 4: IgGs isolated from Myo+SD+ patients alter tissue transcriptomics, mitochondrial content and respiration. | Nature Cardiovascular Research

Fig. 4: IgGs isolated from Myo+SD+ patients alter tissue transcriptomics, mitochondrial content and respiration.

From: An engineered human cardiac tissue model reveals contributions of systemic lupus erythematosus autoantibodies to myocardial injury

Fig. 4

a, Volcano plots depicting the DEGs between tissues cultured with patient IgG from different clinical subgroups. Statistical significance was determined by two-sided Student’s t-test with Benjamini–Hochberg correction for multiple comparisons. Genes that were significantly upregulated (FDR < 0.05) are shown in red, and genes that were significantly downregulated (FDR < 0.05) are shown in blue. b, Venn diagram describing the number of DEGs between tissues treated with IgG from Myo+SD+ patients and IgG from either Myo− patients or Myo+SD− patients and the overlapping DEGs. c, PCA plot of global gene expression profiles for tissues treated with IgG from different patients with SLE and healthy controls. Each point represents the average expression of n = 3 independent tissues treated with IgG from the same patient. d, KEGG analysis of DEGs between tissues treated with IgG from Myo+SD+ patients and IgG from Myo+SD− patients. e, KEGG analysis of cardiomyocyte population DEGs between tissues treated with IgG from Myo+SD+ patients and IgG from Myo+SD− patients. f, Changes in hiPSC-CM mitochondrial quantity in response to patient IgG and measured by the MitoTracker Green probe. Ordinary one-way ANOVA with Dunn’s post hoc comparisons test. g, Changes in SDH activity in hiPSC-CMs in response to patient IgG. Ordinary one-way ANOVA with Tukey’s test for multiple comparisons. h, Characterization of IgG effect on mitochondrial respiration in hiPSC-CMs by Seahorse metabolic flux assay. OCR values were normalized to SDH activity. Ordinary two-way ANOVA with Tukey’s test for multiple comparisons. i, Changes in hiPSC-CM RCR in response to patient IgG. Ordinary one-way ANOVA with Tukey’s test for multiple comparisons. j, Changes in hiPSC-CM mitochondrial membrane potential in response to IgG, measured with the TMRM probe. Ordinary one-way ANOVA with Tukey’s test for multiple comparisons; #P < 0.0001 for comparison of the FCCP group to each other patient group. Data are represented as mean ± s.e.m. n = 3 healthy controls, n = 3 Myo− patients, n = 4 Myo+SD− patients and n = 4 Myo+SD+ patients, with n = 3 independent tissues per patient (a), n = 3 wells per patient (f) or n = 4–6 independent replicate wells per patient sample (g–j). Exact replicate values are included in Supplementary Table 1. Symbol shapes represent different patients within each group. Ctrl, control; FC, fold change; PC, principal component; PV, P value.

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