Table S5 ). (J) Macrophage and myofibroblast abundances, based on deconvolution of bulk-mRNA sequencing (as in I). Treated samples were compared per time point (day 3 or 28), separately by two-tailed unpaired Student t test. Results are represented as mean ± SEM. " width="100%" height="100%">
Journal: Cell Systems
Article Title: Cold and hot fibrosis define clinically distinct cardiac pathologies
doi: 10.1016/j.cels.2025.101198
Figure Lengend Snippet: Cold fibrosis after MI is conserved in humans and in a clinically relevant porcine model (A and B) (A) Representative human left ventricle spatial transcriptomics slides (Visium) of patients following acute-myocardial infarction (MI) and non-transplanted donor hearts. Samples were divided based on time following MI as either: uninjured ( n = 10), early (days 0–15 post-MI; n = 6), and late (30 days+; n = 6). (B) Abundance of fibroblasts and myeloid cells was quantified based on deconvolution scores of cell types per spot . Myofibroblast were calculated as enrichment of the mean myofibroblast state score within spots with a minimal 10% value of cell-type abundance . Statistical analysis used Wilcoxon tests with Benjamini-Hochberg adjusted p values. (C) Experimental design of pig MI experiment: adult (3 months old) pigs underwent MI by temporarily occluding their LAD using a balloon catheter . Following reperfusion (balloon deflation), pigs were immediately treated with recombinant human Agrin (rhAgrin) or Saline control, in an antegrade trajectory. Injured pig hearts were collected at either day 3 ( n = 4 for rhAgrin; n = 3 for Saline) or day 28 ( n = 4 for rhAgrin; n = 3 for saline) and dissected to distinct tissue areas (infarct and remote zones). Remote and infarcted samples were subjected to bulk-mRNA sequencing and histology for fibrosis assessment. (D and E) Representative sirius red staining images are shown from (D) day 3 and (E) day 28 post-MI. Fibrosis was quantified as the average % fold change (FC) between infarct/remote zone sections for each pig individually. Fibrosis (day 3 or day 28) for Saline and rhAgrin hearts was measured using two-tailed unpaired t test. Scale bars: 1 mm. striated line denotes FC = 1. n.s, non-significant difference. (F and G) Heatmaps based on log 2 transformed normalized counts for all (upregulated and downregulated) differentially expressed genes (defined by |log 2 fold change| ≥ 1, p -adjusted value < 0.05 and max raw counts > 30) between remote and infarct zones for Saline and rhAgrin-treated hearts at day 3 (5,961 genes) (F) and 28 (1,079 genes) (G) post-MI. Rows represent genes and columns represent each biological sample and its spatial distribution according to infarct or remote zone. Data are represented as mean ± SD. (H) Hierarchical clustering per condition (day [3 or 28] +treatment [rhAgrin or Saline]), based on the 1,000 most variable genes. Triangles and circles represent remote and infarct zones, respectively. (I) Deconvolution of bulk-mRNA sequencing of pig hearts following MI of either rhAgrin (blue) or Saline-treated (red) samples. Macrophage and myofibroblast abundances were assessed by gene signatures as FC, between infarct and remote zones ( , C, and Table S5 ). (J) Macrophage and myofibroblast abundances, based on deconvolution of bulk-mRNA sequencing (as in I). Treated samples were compared per time point (day 3 or 28), separately by two-tailed unpaired Student t test. Results are represented as mean ± SEM.
Article Snippet: Spatial transcriptomics slides (Visium 10X) of left ventricle tissues of patients with acute myocardial infarction and non-transplanted donor hearts were obtained from Kuppe et al. Labels provided by the original authors describing the distinct pathological zones and time-points after human myocardial infarction were used in the analyses.
Techniques: Recombinant, Saline, Control, Sequencing, Staining, Two Tailed Test, Transformation Assay