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What does your blood remember? The memory of hematopoietic stem cells.

Objective

Human organism produces over a million new blood cells each second. The hematopoietic system dynamically reacts to environmental stress and forms adaptive immunity to memorize and effectively fight the encounter pathogens. However, based on our recent studies and preliminary results, we propose that the adaptive capabilities and memory of the hematopoietic system reach far beyond the classical adaptive antigen-specific immunity.
We hypothesize that hematopoietic stress induces clonal expansion of lineage-biased hematopoietic stem cells (HSCs) with epigenetic memory that faster and more effectively respond to secondary stimulation with a given stress factor. We propose that lineage-biased HSCs accumulating during aging provide a broad adaptive memory of the hematopoietic system, that is not restricted to immune cells, but includes all blood cell lineages.
The aim of our proposal is to understand how the HSC-stored memory is created, maintained and recalled, and to clarify the underlying mechanisms. First, we will selectively stimulate granulopoiesis, erythropoiesis and thrombopoiesis to define the specificity and physiological role of hematopoietic memory provided by HSCs, both in vitro and in vivo. Second, we will use single-cell level fate mapping and sequencing to investigate clonal and epigenetic mechanisms driving the HSCs-based memory in mice. Third, we will test if aging pool of human HSCs consists of lineage-biased HSCs that store memory of the previously encountered stimuli. The humanized mice models will determine the clonal expansion of human HSCs upon primary and secondary stimulation with stress factors.
Altogether, the expected outcome of the project is to understand how and why hematopoietic system adjusts to the environmental challenges upon aging. The proposed novel concept of the hematopoietic system adaptivity may help to design strategies to train patients' hematopoiesis and improve the transplantations of HSCs.

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Keywords

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-STG

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Host institution

UNIWERSYTET JAGIELLONSKI
Net EU contribution

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.

€ 2 500 000,00
Address
UL GOLEBIA 24
31-007 KRAKOW
Poland

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Region
Makroregion południowy Małopolskie Miasto Kraków
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 2 500 000,00

Beneficiaries (1)

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