fig4

Figure 4. Transcriptomic shift in pulmonary aCap ECs induced by Smad4 loss, featuring dysregulated exchange function and activated immune responses. (A) Principal component analysis (PCA) of pulmonary aCap ECs from Smad4^fl/fl and Smad4^iko mice. Note that the two genotypes are separated, suggesting genotype-dependent transcriptomic alterations in aCap ECs. (B) Volcano plots of DEGs in Smad4^iko vs. Smad4^fl/fl pulmonary aCap ECs. Significantly upregulated and downregulated genes are labeled in red and blue. (C) GO enrichment analysis of DEGs from pulmonary aCap ECs. Note that a number of protein folding-related processes and apoptotic pathways are significantly enriched (red lines), reinforcing the notion that SMAD4 maintains proteostasis in ECs. (D) GSEA showing downregulated pathways mapped to proteostasis in Smad4^iko vs. Smad4^fl/fl pulmonary aCap ECs. NES: normalized enrichment score. (E-H) GSEA showing the indicated upregulated pathways linked to exchange function, leukocyte trafficking, calcium homeostasis and barrier architecture regulation in Smad4^iko vs. Smad4^fl/fl pulmonary aCap ECs.