Extracellular vesicle-derived miRNA-mediated cell-cell communication inference for single-cell transcriptomic data with miRTalk.

MicroRNAs are released from cells in extracellular vesicles (EVs), representing an essential mode of cell-cell communication (CCC) via a regulatory effect on gene expression. Single-cell RNA-sequencing technologies have ushered in an era of elucidating CCC at single-cell resolution. Herein, we present miRTalk, a pioneering approach for inferring CCC mediated by EV-derived miRNA-target interactions (MiTIs). The benchmarking against simulated and real-world datasets demonstrates the superior performance of miRTalk, and the application to four disease scenarios reveals the in-depth MiTI-mediated CCC mechanisms. Collectively, miRTalk can infer EV-derived MiTI-mediated CCC with scRNA-seq data, providing new insights into the intercellular dynamics of biological processes.