Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction

Lukas S. Tombor, David John, Simone F. Glaser, Guillermo Luxán, Elvira Forte, Milena Furtado, Nadia Rosenthal, Nina Baumgarten, Marcel H. Schulz, Janina Wittig, Eva-Maria Rogg, Yosif Manavski, Ariane Fischer, Marion Muhly-Reinholz, Kathrin Klee, Mario Looso, Carmen Selignow, Till Acker, Sofia-Iris Bibli, Ingrid Fleming, Ralph Patrick, Richard P. Harvey, Wesley T. Abplanalp and Stefanie Dimmeler ()
Additional contact information
Lukas S. Tombor: Goethe University Frankfurt
David John: Goethe University Frankfurt
Simone F. Glaser: Goethe University Frankfurt
Guillermo Luxán: Goethe University Frankfurt
Elvira Forte: The Jackson Laboratory
Milena Furtado: The Jackson Laboratory
Nadia Rosenthal: The Jackson Laboratory
Nina Baumgarten: Goethe University Frankfurt
Marcel H. Schulz: Goethe University Frankfurt
Janina Wittig: Goethe University Frankfurt
Eva-Maria Rogg: Goethe University Frankfurt
Yosif Manavski: Goethe University Frankfurt
Ariane Fischer: Goethe University Frankfurt
Marion Muhly-Reinholz: Goethe University Frankfurt
Kathrin Klee: German Center of Cardiovascular Research (DZHK)
Mario Looso: Cardiopulmonary Institute
Carmen Selignow: University Giessen
Till Acker: Cardiopulmonary Institute
Sofia-Iris Bibli: Goethe University Frankfurt
Ingrid Fleming: Cardiopulmonary Institute
Ralph Patrick: Victor Chang Cardiac Research Institute
Richard P. Harvey: Victor Chang Cardiac Research Institute
Wesley T. Abplanalp: Goethe University Frankfurt
Stefanie Dimmeler: Goethe University Frankfurt

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20905-1

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DOI: 10.1038/s41467-021-20905-1

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