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

  • 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.

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Author:Lukas TomborORCiDGND, David JohnORCiDGND, Simone F. GlaserORCiDGND, Guillermo LuxánORCiD, Elvira ForteORCiD, Milena Furtado, Nadia Rosenthal, Nina BaumgartenORCiDGND, Marcel Holger SchulzORCiDGND, Janina Wittig, Eva-Maria Pia RoggGND, Yosif Manavski, Ariane Fischer, Marion Muhly-Reinholz, Kathrin KleeORCiD, Mario LoosoORCiDGND, Carmen Selignow, Till AckerORCiDGND, Sofia Iris BibliORCiD, Ingrid FlemingORCiDGND, Ralph PatrickORCiD, Richard P. Harvey, Wesley Tyler AbplanalpORCiD, Stefanie DimmelerORCiDGND
Parent Title (German):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Date of Publication (online):2021/01/29
Date of first Publication:2021/01/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/02/04
Issue:Article 681
Page Number:12
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0