Objective
How hematopoietic stem and progenitor cells (HSPCs) regenerate blood is a major unsolved question, frustrating their effective use for therapy. Every year, >40.000 patients receive an HSPC transplantation (HSCT), as a last-resort therapy for various diseases, including leukemia. However, ~40% of HSCT recipients die, due to poor outgrowth of the donor HSPCs, inflammatory complications or relapse. There is an unmet need for strategies to predict and prevent these adverse outcomes. In mice, single-cell methods have revolutionized our understanding of how hematopoiesis is organized, allowing us to control the outcome of murine HSCT in detail. In contrast, our understanding of human hematopoietic regeneration, and our ability to control this process, is lagging behind. As a clinician in pediatric HSCT and stem cell biologist, my mission is to change this. RESTART aims to comprehensively characterize the cellular and molecular mechanisms guiding hematopoietic regeneration in humans. I have pioneered single-cell methods to study human HSPC biology. Here, we will apply state-of-the-art multiomics to dissect the identities and functional states of thousands of HSPCs and their surrounding niche cells in human bone marrow (BM). Embedded in Europe’s largest pediatric cancer center, we will apply these methods to a unique, longitudinal collection of BM samples of pediatric HSCT recipients and their donors, collected before and up to a year after HSCT. Our objectives are: (1) Dissect the cellular and molecular composition of the HSPC population during successful hematopoietic regeneration in human HSCT recipients; (2) Determine how HSCT-induced alterations in BM niche cells affect HSPC fate; (3) Leverage this information to identify and validate single-cell states or trajectories predictive of adverse HSCT outcome (graft failure, relapse). This study will contribute to improved survival of human HSCT recipients and to increased fundamental knowledge on human tissue regeneration.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine transplantation
- medical and health sciences clinical medicine oncology leukemia
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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)
MAIN PROGRAMME
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Topic(s)
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.
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-STG
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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.
3584CS Utrecht
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.