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RESTART

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How is blood (re-)made? Regeneration of human hematopoietic stem cells after tra...

How is blood (re-)made? Regeneration of human hematopoietic stem cells after transplantation 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... ver más

31/12/2028

PrinsesMaximaCentr...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE B... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-10-12

ERC-2023-STG: ERC STARTING GRANTS Scope:Objectives

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PrinsesMaximaCentrumvoorKind...

1.50M€ | Lider

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Duración del proyecto: 62 meses Fecha Inicio: 2023-10-12
Fecha Fin: 2028-12-31

Líder del proyecto

PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE B... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto 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.

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