Multi-omic analysis of serial-cultured human iPSC-derived MSC with lamin A/C mutation reveals miR-311 as a potential biomarker of senescent cells

Pathogenic mutations in lamin A/C (LMNA) lead to nuclear structural abnormalities, mesenchymal tissue damage, and laminopathies, which have numerous tissue-specific and progeria phenotypes. However, how LMNA mutations lead to accelerated mesenchymal-derived cell senescence remains unclear. Here, we found that the effects of young MSC-EV and senescent MSCP-EV on LMNA R527C iMSC senescence were inconsistent. To find out the essential elements during exosome treatment, we performed miRNA sequencing of exosomes derived from LMNA R527C MSCs, and identified MSC-EVs could promote surrounding cell senescence via carrying high levels of pro-senescence miRNAs, among which the novel miRNA (called miR-311) could be used as a new indicator to detect chronic and acute MSC senescence and play a role in promoting senescence.