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March 2021

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Single cell sequencing reveals endothelial plasticity with transient mesenchymal activation after myocardial infarction. Nature Communications (2021). DZHK authors: Lukas S. Tombor, David John, Simone F. Glaser, Guillermo Luxán, Nina Baumgarten, Marcel H. Schulz, Janina Wittig, Yosif Manavski, Kathrin Klee, Sofia-Iris Bibli, Ingrid Fleming, Wesley T. Abplanalp, Stefanie Dimmeler

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Endothelial cells play a crucial role when tissues adapt to injury. After tissue ischemia induced by infarction, they can clonally expand, adapt their metabolism, and migrate. This phenotypic change has been associated with the expression of mesenchymal genes, but whether these cells contribute to the pool of fibroblasts in the long term and yet to fibrosis has not been clear.

In a study published in Nature Communications, DZHK scientists at Goethe University Frankfurt showed, by using single-cell sequencing, that endothelial cells transiently express mesenchymal genes within the first days after a heart attack. This is accompanied by metabolic adaptation, proliferation, and TGF-ß signalling. However, at later stages, these cells do not acquire a long-term mesenchymal fate but revert to an endothelial fate. Therefore, the researchers termed this process EndMA (Endothelial to Mesenchymal Activation), which might be required for facilitating tissue regeneration. This “activation” (EndMA) is notably different from other examples where cells undergo a complete transition, such as epithelial to mesenchymal transition or heart valve morphogenesis.

Using in vitro models, scientists could mimick this reverting phenotype by the simple withdrawal of TGF-ß. Epigenetically, DNA methylation patterns were also transiently changed, suggesting that endothelial cells do not undergo actual fate changes.
Understanding long-term changes in interstitial cells in the heart is an important factor for developing future therapeutic interventions after cardiac injury. To which extend EndMA could also occur in other disease conditions should be investigated in further studies.

Link to Paper