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Cell size as driver of stem cell aging and cancer

Project description

Ageing: does cell size matter?

Cell size maintenance is crucial for proper cellular function and is tightly regulated in living organisms. Cells have specific mechanisms to control their size, ensuring they stay within certain dimensions optimal for their functions. Funded by the European Research Council, the StemCellSize project proposes the hypothesis that a change in stem cell size may be linked to ageing. To delineate this, researchers will study how cellular enlargement in stem cells during ageing can lead to dysfunction and the development of cancer. The work will focus on haematopoietic stem cells and their size-fitness relationship during ageing, shedding light on a previously unexplored topic.

Objective

The failure to regenerate tissue underlies a challenging health issue in elderly. A main contributor to this decline is the loss of stem cell function during aging. Despite the essential role of stem cells, it is unclear how they fail to maintain their functions during aging and disease. I discovered a new aspect of stem cell aging in vivo: cellular enlargement. With age, stem cells increase in size leading to their functional decline. However, it is unclear how size impacts stem cell fitness. Moreover, the physiological importance of this process remains unsolved.

My team at the University of Helsinki will address these questions by: (1) identifying pathways that promote stem cell dysfunction during enlargement, (2) assessing the effects of size reduction on stem cell rejuvenation, and (3) illuminating the effects of stem cell size on cancer.

Supported by preliminary data, I hypothesize that cell size is a driver of stem cell aging and cancer. Using hematopoietic stem cells (HSCs) of mouse models, I will identify the molecular mechanisms impairing fitness of large HSCs. I will also perform a screen to identify pathways that modulate the size of HSCs to test for rejuvenation. These will allow me to establish how HSC size affects other cellular aging pathways, organismal health and whether this relationship is causal or correlative. I hypothesize that cellular size impacts HSCs to transform into cancerous cells. To test this, I will use differently sized, oncogenic HSCs from mice and humans to test their potential to facilitate leukemia in vivo and to investigate the underlying mechanisms of this process.

The novel concepts outlined here have exceptional potential for scientific impact as they add a new paradigm to stem cell aging, provide transformative treatment perspectives and examine cancer from a new dimension.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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-2023-STG

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Host institution

HELSINGIN YLIOPISTO
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.

€ 1 500 000,00
Address
FABIANINKATU 33
00014 HELSINGIN YLIOPISTO
Finland

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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.

€ 1 500 000,00

Beneficiaries (1)

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