Fig. 2

Exploring possible bioactivity of TSC-EVs in MicroRNA profiling (A) Venn diagram comparing the different compositions of small RNAs identified in TSC- and MSC-EV. B Differentially expressed microRNAs in TSC-EV compared with MSC-EV were represented by the volcano plot based on fold-change (FC) and p values (|FC|≥ 1.5 adjusted with p < 0.05). C Up- or downregulated microRNAs in TSC-EV verified the microRNA profiling results via quantitative RT-PCR. D Top 10 microRNAs in each stem cells-derived EV were presented by graph. The most abundant top 4 microRNAs in TSC-EV were indicated by the red color. E Enrichment map of biological effects targeted by the four microRNAs overexpressed in TSC-EV. The connection nodes indicate significantly enriched biological processes and pathways (p < 0.05). F STRING analysis presented six functional clusters, stem cell regulation, Hippo signaling, Wnt signaling, brain development, DNA-binding transcription activation, and amyloid-beta binding, regulated by predicted targets of four overexpressed microRNAs in TSC-EV. G DAVID analysis revealed differential changes in enriched KEGG pathway caused by four microRNAs overexpressed in TSC-EV, compared with KEGG pathway of top 1% microRNAs expressed in MSC-EV (enriched in TSC-EV, yellow; enriched in MSC-EV, blue)