Fig. 4

Adra1 activates an “extracellular matrix (ECM) remodeling” transcriptional program in a macrophage subset (A) Diagram showing mixed populations of control (adra1-3i-T2A-CFP−) and Adra1-signaling-deficient (adra1-3i-T2A-CFP+) macrophages present in the same cryoinjured heart. (B) t-distributed stochastic neighbor embedding (t-SNE) representation of whole-heart single-cell clustering. Dashed line outlines all macrophage/monocyte populations. A pool of 3 hearts was analyzed. (C) t-SNE dimensionality reduction representation of 4 clusters in the adra1-3i-T2A-CFP– and 3 clusters in adra1-3i-T2A-CFP+ populations. (D) Heatmap of the 70 most differentially expressed genes in each cluster from (C) showed comparable expression profiles of the shared clusters (clusters 1–3), and cluster-defining genes of cluster 4 (ECM remodeling), present only in the adra1-3i-T2A-CFP– macrophage pool. (E) Violin plots of cluster-defining genes depicted in (D). (F) Gene ontology (GO) enrichment of differentially up- (activated) and downregulated (suppressed) genes in the Adra1-signaling-deficient (adra1-3i-T2A-CFP+) versus control (adra1-3i-T2A-CFP–) macrophages, displayed as gene ratio (differentially expressed genes related to GO term/total number of differentially expressed genes). Dot size in the graph represents number of differentially expressed genes enriched in a GO term (count). Bonferroni-Holm adjusted p values are represented with color scale of the dots.