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EpiHTStem

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Understanding the Maintenance and Heritability of Hematopoietic Stem Cell Memori...

Understanding the Maintenance and Heritability of Hematopoietic Stem Cell Memories High Throughput Drug Screening Meets Single Cell Barcoding During the development of multicellular organisms, cells from the same niche can be stochastically exposed to different signals and stimuli, and this variability has the potential to create epigenetic heterogeneity across cell pop... ver más

31/03/2025

FUNDACIO INSTITUT...

165K€

Presupuesto del proyecto: 165K€

Líder del proyecto

FUNDACIO INSTITUT DE RECERCA BIOMEDICA IRB BA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 23M€

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-03-13

HORIZON-MSCA-2022-PF-01-01: MSCA Postdoctoral Fellowships 2022 ExpectedOutcome:

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165.31K€ | Lider

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Duración del proyecto: 24 meses Fecha Inicio: 2023-03-13
Fecha Fin: 2025-03-31

Líder del proyecto

FUNDACIO INSTITUT DE RECERCA BIOMEDICA IRB BA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 23M€

Presupuesto del proyecto 165K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto During the development of multicellular organisms, cells from the same niche can be stochastically exposed to different signals and stimuli, and this variability has the potential to create epigenetic heterogeneity across cell populations. Importantly, this heterogeneity can confer individual cells different functional properties or different capacities to respond to the same stimuli. During the last decade, multiple laboratories have reported the existence of hematopoietic stem cell (HSC) clones with different functional behaviors that are transmitted to daughter cells. Very interestingly, these behaviors are transmitted to their progeny even after transplantation, suggesting that heritable epigenetic components are required to establish and maintain them. In this regard, some questions arise: Which epigenetic regulators are involved in the maintenance of these memories? Which regions associate with specific HSC fate memories? And, how heritable are different chromatin states in dividing HSCs? Until recently, we were very limited by the current technologies to answer these questions. Now, recent advances in single-cell lineage tracing, single-cell multiomics and ex-vivo HSC expansion cultures can be leveraged to provide a robust mechanistic understanding of clonal heritability of HSC fates and states. Consequently, this proposal aims to combine new lineage tracing techniques, multimodal single-cell sequencing and functional assays to: (1) create an atlas of clonally-heritable epigenetic states associated to specific functional HSC behaviors and (2) to identify epigenetic regulators that are required to maintain and transmit HSC memories associated with specific HSC fates.

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