SubsidieMeestersThe Interplay of Aging, Immune Signaling and Stem Cell Function
This project aims to investigate how immune environment changes contribute to muscle stem cell dysfunction and regenerative decline in aging, with the goal of improving stem cell therapies.
Projectdetails
Introduction
Adult stem cells (SCs) sustain tissue renewal and repair throughout life. The SC niche is fundamental in the regulation of SC function and an important contributor to SC decline in aging. While alterations in the tissue’s immune environment are emerging as important contributors to impairments found in aged organs, their contribution to SC dysfunction in aging is unknown.
Background
The skeletal muscle (SkM) is a paradigmatic model to study age-related loss of repair capacity. Muscle stem cell (MuSC) function during regeneration requires plasticity in transit between states of quiescence, activation, and differentiation. MuSC functional impairments in aging result from changes in the extrinsic cues that govern their behavior, but also cell intrinsic alterations, including senescence and defects in lineage commitment. However, we still have a limited understanding of how changes in the environment manifest as SC intrinsic defects.
Previous Work
Our previous work indicates that changes in immune signaling are important drivers of MuSC dysfunction and regenerative decline in aging.
Research Aims
Here, we propose to identify the contribution of specific immune populations and signals to changes in regenerative capacity and MuSC activity in aging (Aim 1). We hypothesize that the immune environment is an essential regulator of MuSC plasticity and lineage commitment under regenerative pressure, and immune alterations underlie defects in MuSC lineage fidelity in aging.
- Aim 1: Identify the contribution of specific immune populations and signals to changes in regenerative capacity and MuSC activity in aging.
- Aim 2: Map the trajectories of MuSCs diverging from the myogenic lineage and uncover the changes in epigenetic landscape that underlie the loss of lineage fidelity associated with immune aging, identifying transcriptional regulators of MuSC fate.
- Aim 3: Test the knowledge generated on the mechanisms linking immune aging and MuSC dysfunction for conservation in human SkM and apply it to improve the success of MuSC-based therapies in aging.
The knowledge generated on the mechanisms linking immune aging and MuSC dysfunction will be tested for conservation in human SkM and will be applied to improve the success of MuSC-based therapies in aging.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.998.843 |
| Totale projectbegroting | € 1.998.843 |
Tijdlijn
| Startdatum | 1-3-2024 |
| Einddatum | 28-2-2029 |
| Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- FUNDACAO GIMM - GULBENKIAN INSTITUTE FOR MOLECULAR MEDICINEpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
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Stem and niche cell dynamics in normal and pathological conditions
This project investigates how skeletal muscle stem cells respond to distant pathologies, aiming to uncover new insights into stem cell behavior and tissue regeneration using advanced multiomics and imaging techniques.
Mutations in healthy tissues: a double-edged sword for tissues homeostasis
This project investigates how somatic mutations enhance the fitness of stem/progenitor cells to maintain tissue integrity and regenerative potential, linking ageing, mutations, and disease risk.
The impact of human aged bone marrow niche on human hematopoietic stem cell function
This project aims to investigate how aging alters the human bone marrow niche and its impact on hematopoietic stem cell function to improve understanding and outcomes in elderly hematopoiesis.
Cell size as driver of stem cell aging and cancer
This project aims to investigate how cellular enlargement affects stem cell function and aging, potentially linking size to rejuvenation and cancer development, using mouse models for insights.
In vivo metabolic determinants of T cell aging trajectories
This project aims to uncover how aging microenvironments affect T cell immunity and explore methods to rejuvenate T cells to combat age-related diseases.