TY - JOUR A1 - Tombor, Lukas A1 - John, David A1 - Glaser, Simone F. A1 - Luxán, Guillermo A1 - Forte, Elvira A1 - Furtado, Milena A1 - Rosenthal, Nadia A1 - Baumgarten, Nina A1 - Schulz, Marcel Holger A1 - Wittig, Janina A1 - Rogg, Eva-Maria Pia A1 - Manavski, Yosif A1 - Fischer, Ariane A1 - Muhly-Reinholz, Marion A1 - Klee, Kathrin A1 - Looso, Mario A1 - Selignow, Carmen A1 - Acker, Till A1 - Bibli, Sofia Iris A1 - Fleming, Ingrid A1 - Patrick, Ralph A1 - Harvey, Richard P. A1 - Abplanalp, Wesley Tyler A1 - Dimmeler, Stefanie T1 - Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction T2 - Nature Communications N2 - Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network. Y1 - 2021 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57745 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-577456 SN - 2041-1723 VL - 12 IS - Article 681 PB - Nature Publishing Group UK CY - [London] ER -