Fig. 3

Transcriptomic analysis of TSC-EV-induced regenerative capacity on MSCs. A MDS plot of RNA-seq result represents the distinct cluster correspond to the differences in differentially expressed genes (DEG) between MSCs (red) and TSC-EV-treated MSCs (blue). The three replicates in each group show the close distance. B The heatmap clustering data visualize the change in differential gene expression levels across TSC-EV-treated MSCs compared with untreated control MSCs values (|FC|≥ 1.5 adjusted with p < 0.05). C The Volcano plot indicates differentially expressed up- and downregulated genes in response to TSC-EV treatment on MSCs. The numbers of significantly up- and downregulated genes are denoted. D Significant KEGG pathways enriched in TSC-EV-treated MSCs are showed by table with the statistical scores (FDR and p-value) and the number of significant genes. E The enriched molecular function in TSC-EV-treated MSCs is showed with adjusted p-value and gene expression ratio. F Gene set enrichment analysis (GSEA) in MSCs [A] and TSC-EV-treated MSCs [B] were subjected with enrichment score based on significance. Regeneration activity of MSCs related four enrichment plots are presented with up- or downregulated genes in each data set. G Heatmaps present DEG levels enriched to core biological processes or pathways in (F). DEGs associated with ossification, wound healing, and cytokine regulation were preferentially expressed in TSC-EV-treated MSCs gene expression profile. Negative correlation of Adipogenesis DEGs was analyzed in TSC-EV-treated MSCs enriched genes