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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Knight-Schrijver, Vincent R  ORCID logo  https://orcid.org/0000-0002-7916-3827
Davaapil, Hongorzul 
Bayraktar, Semih 
Ross, Alexander DB 
Kanemaru, Kazumasa 

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.

Description

Keywords

Cambridge Stem Cell Institute

Journal Title

Nat Cardiovasc Res

Conference Name

Journal ISSN

2731-0590
2731-0590

Volume Title

Publisher

Nature
Sponsorship
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (203151/A/16/Z)
British Heart Foundation (None)
British Heart Foundation (RG/17/5/32936)
British Heart Foundation (PG/17/24/32886)
British Heart Foundation (FS/18/46/33663)
British Heart Foundation (via University of Oxford) (AVR02740)