Extended Data Fig. 1: General features of sEV secretion among the five cell types studied.

a) Number of vesicles over 48 h released by each cell type normalized by the number of cells in the tissue-culture plate (n=4). *P≤0.05 (indicated cell type versus all other cell types), § P≤0.05 (indicated cell type versus 3T3-L1, C2C12 and SVEC) (Kruskal-Wallis followed by Mann-Whitney U test). b) Average vesicle size of the sEV as determined by Nanoparticle tracking analysis (NTA) for each cell type (n=4). c) Average size distribution and number of vesicles released per cell for each of the five cell types. d) Immunoblotting for the indicated sEV (ALIX, TSG101 and CD9) and cellular (GM130, CANX) markers in sEV and cell lysates from AML12 hepatocytes and BAT brown adipocytes. e) Electron micrograph showing CD63 gold immunostaining of sEV isolated from C2C12 cells. f) RNA yield obtained from sEV isolated from each cell type and normalized by the number of cells in the tissue-culture plate (n=3). *P≤0.05 (indicated cell type versus all other cell types); § P≤0.05 (indicated cell type versus 3T3-L1 and BAT) (Kruskal-Wallis followed by Mann-Whitney U test). g) Principal component analysis showing cellular miRNA profiles for each cell type. h) Heatmap showing the top 10 representative cellular miRNAs of each cell type. i) Heatmap showing the top 10 representative sEV miRNAs of each cell type. j) Comparative miRNA profile between cell-derived sEV and non-conditioned medium (NCM). Same volume of NCM as in cell-conditioned medium was processed for sEV isolation by differential ultracentrifugation. RNA was isolated and a miRNA profiling was performed for NCM. The miRNA expressions for the 13 miRNAs found sEV-enriched in all 5 cell types were compared to the NCM average Ct by ΔΔct method and represented as fold change. Each dot is the relative average value of each of the five cell types. Data are expressed as mean ± SEM.