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FUN-HSC

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TACKLING FUNCTIONAL MATURATION FOR TRANSPLANTABLE HEMATOPOIETIC STEM CELL GENERA...

TACKLING FUNCTIONAL MATURATION FOR TRANSPLANTABLE HEMATOPOIETIC STEM CELL GENERATION Hematopoietic stem cells (HSC) provide a lifelong supply of blood and immune cells. They are a life-saving therapy for leukemia and have recently found broadened applications to gene and cell therapy, against other cancers, geneti... ver más

31/12/2028

FUNDACIO INSTITUT...

2M€

Presupuesto del proyecto: 2M€

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FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEM... Actividades de investigación asociacion

TRL 4-5 | 50K€

Ver 2 Participantes

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-11-15

ERC-2022-COG: ERC CONSOLIDATOR GRANTS Scope:Objectives

I+D

Cerrada hace 2 años

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2 Participantes

FUNDACIO INSTITUT DE RECERCA...

2.07M€ | Lider

UNIVERSITY COLLEGE LONDON

199.90K€ | Participante

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Duración del proyecto: 61 meses Fecha Inicio: 2023-11-15
Fecha Fin: 2028-12-31

Líder del proyecto

FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEM... Actividades de investigación asociacion

TRL 4-5 | 50K€

Presupuesto del proyecto 2M€

Descripción del proyecto Hematopoietic stem cells (HSC) provide a lifelong supply of blood and immune cells. They are a life-saving therapy for leukemia and have recently found broadened applications to gene and cell therapy, against other cancers, genetic, autoimmune, and infectious diseases. Nonetheless, practical limitations, such as donor-matching or insufficient cell number render these therapies unfeasible or unsuccessful for many patients. Attempts to overcome these limitations have been unable to create a reliable source of HSC for patients: while we can generate human HSC from pluripotent stem cells (PSC), they resemble early development stages, lacking the functional maturation hallmarks. FUN-HSC aims at identifying core and actionable maturation pathways for HSCs and at defining the contribution of coordinated gene expression by chromatin regulation, using a combination of functional and genetic screening technologies and high-throughput readouts in vitro and in vivo. HSC maturation occurs in the liver during fetal development and confers functional multilineage hematopoiesis ability throughout adulthood. Using single cell omics analysis of human embryonic and fetal tissues, we describe multiple gene programs changing during developmental HSC maturation. This study will lead to candidate cell-intrinsic and niche-dependent instructions, which will be dissected in the context of the fetal liver, by analyzing the cell compartments and their interactions and by combining novel organoid technologies with mouse xenografts to model the fetal liver environment. Ultimately, we aim to identify a strategy that mimics these pathways in vitro to bring the maturation stage of the PSC-derived HSC, to a robustly engraftable and clinically valuable HSC source. Harnessing new knowledge in human HSC biology, cutting-edge genetics and tissue technologies, FUN-HSC will provide great advances in the mission of making and maintaining HSCs in vitro, enabling their full therapeutic potential.

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