title: Characterisation of the human embryonic and foetal epicardium during heart development.
abstract: The epicardium is essential for mammalian heart development. At present, our understanding of the timing and morphogenetic events leading to the formation of the human epicardium has essentially been extrapolated from model organisms. Here, we studied primary tissue samples to characterise human epicardium development. We reveal that the epicardium begins to envelop the myocardial surface at Carnegie stage (CS) 11 and this process is completed by CS15, earlier than previously inferred from avian studies. Contrary to prevailing dogma, the formed human epicardium is not a simple squamous epithelium and we reveal evidence of more complex structure, including novel spatial differences aligned to the developing chambers. Specifically, the ventricular, but not atrial, epicardium exhibited areas of expanded epithelium, preferential cell alignment and spindle-like morphology. Likewise, we reveal distinct properties ex vivo, such that ventricular cells spontaneously differentiate and lose epicardial identity, whereas atrial-derived cells remained 'epithelial-like'. These data provide insight into the developing human epicardium that may contribute to our understanding of congenital heart disease and have implications for the development of strategies for endogenous cell-based cardiac repair.
authors.affiliation: UCL-Institute of Child Health, Molecular Medicine Unit, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Risebro
authors.affiliation: University of Oxford, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford OX1 3PT, UK.
authors.forename: Joaquim Miguel
authors.initials: JM
authors.lastname: Vieira
authors.affiliation: UCL-Institute of Child Health, Molecular Medicine Unit, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Klotz
authors.affiliation: UCL-Institute of Child Health, Molecular Medicine Unit, 30 Guilford Street, London WC1N 1EH, UK University of Oxford, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford OX1 3PT, UK paul.riley@dpag.ox.ac.uk.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Riley
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005333:Fetus / Q000033:anatomy & histology / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D006330:Heart Defects, Congenital / Q000378:metabolism; D006801:Humans; D007633:Keratins; D009206:Myocardium / Q000166:cytology; D038081:Organogenesis
chemical_list: D007633:Keratins
keywords: Epicardium; Epithelial-to-mesenchymal transition; Heart; Human; Regeneration