Single-cell analysis reveals a novel regulatory mechanism of endothelial-to-mesenchymal transition

The transdifferentiation of endothelial cells (ECs) towards a mesenchymal-like phenotype, referred to as endothelial-to-mesenchymal transition (EndMT), is critical for embryonic development, and in adults it is one of the major contributors to the onset of diseases, including cancer, fibrosis and a number of cardiovascular disorders. Here we identified mitochondrial calcium signaling as a key regulator of EndMT in three in vitro EndMT models, as well as in physiopathological conditions in vivo. Pharmacological inhibition of the mitochondrial calcium uniporter (MCU) prevents EndMT. Deletion of MCU in ECs confirms loss of EndMT during cardiac embryo development as well as in a hind limb ischemia mouse model. Together, our data provide evidence of a novel regulatory mechanism of endothelial transdifferentation, thus potentially allowing for the development of new therapeutic interventions for EndMT-related diseases.