A single-cell comparison of adult and fetal humen epicardium defines the 
age-associated changes in epicardial activity

Knight-Schrijver, Vincent R.; Davaapil, Hongorzul; Bayraktar, Semih; Ross, Alexander D. B.; Kanemaru, Kazumasa; Cranley, James; Dabrowska, Monika; Patel, Minal; Polanski, Krzysztof; He, Xiaoling; Vallier, Ludovic; Teichmann, Sarah; Gambardella, Laure; Sinha, Sanjay

doi:10.1038/s44161-022-00183-w

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A single-cell comparison of adult and fetal humen epicardium defines the age-associated changes in epicardial activity

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Vallier, Ludovic
Liver Organogenesis (Ludovic Vallier), Max Planck Fellow Group, Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Knight-Schrijver, V. R., Davaapil, H., Bayraktar, S., Ross, A. D. B., Kanemaru, K., Cranley, J., et al. (2022). A single-cell comparison of adult and fetal humen epicardium defines the age-associated changes in epicardial activity. Nature Cardiovascular Research, 1, 1215-1229. doi:10.1038/s44161-022-00183-w.

Cite as: https://hdl.handle.net/21.11116/0000-000D-30F1-C

Abstract

Re-activating quiescent adult epicardium represents a potential therapeutic approach for human cardiac regeneration. However, the exact molecular differences between inactive adult and active fetal epicardium are not known. In this study, we combined fetal and adult human hearts using single-cell and single-nuclei RNA sequencing and compared epicardial cells from both stages. We found that a migratory fibroblast-like epicardial population only in the fetal heart and fetal epicardium expressed angiogenic gene programs, whereas the adult epicardium was solely mesothelial and immune responsive. Furthermore, we predicted that adult hearts may still receive fetal epicardial paracrine communication, including WNT signaling with endocardium, reinforcing the validity of regenerative strategies that administer or reactivate epicardial cells in situ. Finally, we explained graft efficacy of our human embryonic stem-cell-derived epicardium model by noting its similarity to human fetal epicardium. Overall, our study defines epicardial programs of regenerative angiogenesis absent in adult hearts, contextualizes animal studies and defines epicardial states required for effective human heart regeneration.