Project description
Epicardium development for human heart regeneration
Cardiac diseases are a leading cause of death globally, highlighting the critical need for human cardiac regeneration. The epicardium, a source of cardiac cells, plays a crucial role in heart development and repair. However, our understanding of human epicardium development and its response to injury remains limited. Advances in pluripotent stem cell-based cardiac organoids, known as epicardioids, provide an opportunity to study human epicardium development at single-cell resolution. The ERC-funded EPICURE project aims to decode and leverage the biological programmes that could revolutionise human heart regeneration. The project will use cutting-edge techniques such as lineage recordings, 3D imaging, and spatial multiomics in epicardioids to investigate the embryonic epicardium, identify signalling pathways, and explore the potential for heart regeneration in adulthood.
Objective
Cardiac diseases are the leading cause of death worldwide, making human cardiac regeneration one of the most critical unmet clinical needs. The epicardium, the mesothelial envelope of the heart, is the source of several cardiac cells and provides signals that are essential for myocardial growth and vessel formation during development. Extensive animal research has indicated that the reactivation of these embryonic epicardial programs is the key to adult tissue repair in regenerative species such as the zebrafish, as well as in rodents up until a few days after birth, before the heart’s capacity for regeneration is lost. How the human epicardium develops and responds to injury is largely unknown. We recently established the first human pluripotent stem cell-based cardiac organoids showing the self-organization of epicardium and myocardium into a functionally patterned structure resembling the embryonic ventricular wall. These ‘epicardioids’ offer unique possibilities to study the dynamics of human epicardium development and function at a single-cell resolution. EPICURE aims at decoding and harnessing these programs as potentially transformative means for human heart regeneration. State-of-the-art lineage recordings, 3D imaging, and spatial multiomics in epicardioids will be used to dissect the fate acquisition mechanisms of the human embryonic epicardium and identify critical signalling pathways in health and disease. This in vitro approach will be complemented by charting a spatiotemporal, cross-species single-cell atlas of the cardiac injury response ex vivo and in vivo, including the first genetic lineage tracing of the adult epicardium in a large animal model. Finally, we will capitalize on the novel concept that CRISPR-mediated, temporal programming of the epicardium could drive meaningful heart regeneration in adulthood. Clearly, EPICURE will yield a wealth of new insights into human epicardial biology while breaking new ground in cardiac regenerative medicine.
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
81675 MUENCHEN
Germany
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