MSCs with upregulated lipid metabolism block hematopoietic stem cell differentiation via exosomal CTP-1A in MDS

• MDS-derived MSCs exhibit functional impairments including reduced proliferation, impaired differentiation, diminished hematopoietic support, and increased apoptosis. • Upregulation of lipid metabolism in MDS-MSCs contributes to their dysfunction, and can be reversed by etomoxir (ETO), a CPT-1A inhibitor. • MDS-MSCs transmit dysfunction to HSCs via exosomes enriched in CPT-1A, revealing a novel MSCs-metabolism-exosome axis. • Targeting CPT-1A or exosomal CPT-1A may offer new therapeutic strategies for MDS.