Fig. 5: Coronary artery lineage of VSMCs uniquely expresses an inflammatory network.
From: A CRISPR/Cas9-based enhancement of high-throughput single-cell transcriptomics

a Genes with the highest correlation associated with each terminal state. Average gene expression sampled from 200 cells with an absorption probability >0.5 associated with each lineage (pulmonary lineage = top, coronary lineage = bottom) and mapped along pseudotime. b Dendrograms representing the principal graph (scFATES) inferred from scCLEAN terminal states. (left) Blue represents early pseudotime and yellow represents late pseudotime. (right) Cells colored according to arterial origin (coronary =  red, pulmonary = gray) projected along pseudotime. c Tree diagram highlighting onset of characteristic gene signatures (red) associated with pulmonary lineage (top) and coronary lineage (bottom). d Gene expression heatmaps of highest specificity (effect > 0.3) depicting early root cells (left), coronary lineage (middle), and pulmonary lineage (right). The smoothed gene expression is shown along pseudotime and colored by expression (low = blue and high = red). Gene specific pseudo-temporal activation to the pulmonary lineage (top; n = 91) and to the coronary lineage (bottom, n = 32). The top 15 genes for each arterial origin are depicted. e Feature plots of log(x + 1) normalized expression on the FLE embedding comparing the expression of 3 representative lineage markers specific to the pulmonary (top) and coronary (bottom) lineages. f Gene transition heatmap of top markers for the pulmonary (top) and coronary (bottom) bifurcation to reflect early decision-making processes prior to separation. The matrix contains inclusion timing for each gene in each probabilistic lineage projection. g Z-scored mean expression of inflammatory genes comparing coronary and pulmonary across three equivalent bins of pseudotime (early, middle, late). h The top five enriched lineage-specific pathways found using GSEA with all lineage-specific genes (correlation greater than 0.3). The combined score (y-axis) incorporates gene overlap and statistical significance. i Top regulons with differential expression between coronary and pulmonary lineages. Binarized regulon activity (SCENIC).