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.
- Immune alterations underlie defects in MuSC lineage fidelity in aging.
We propose to 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 2).
Application of Knowledge
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 (Aim 3).
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 |
|---|---|---|---|---|
MANUNKIND: Determinants and Dynamics of Collaborative ExploitationThis project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery. | ERC STG | € 1.497.749 | 2022 | Details |
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressureThe UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance. | ERC STG | € 1.498.280 | 2022 | Details |
Uncovering the mechanisms of action of an antiviral bacteriumThis project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function. | ERC STG | € 1.500.000 | 2023 | Details |
The Ethics of Loneliness and SociabilityThis project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field. | ERC STG | € 1.025.860 | 2023 | Details |
MANUNKIND: Determinants and Dynamics of Collaborative Exploitation
This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure
The UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance.
Uncovering the mechanisms of action of an antiviral bacterium
This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.
The Ethics of Loneliness and Sociability
This project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field.
Vergelijkbare projecten uit andere regelingen
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Stem and niche cell dynamics in normal and pathological conditionsThis 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. | ERC ADG | € 2.499.600 | 2022 | Details |
In vivo metabolic determinants of T cell aging trajectoriesThis project aims to uncover how aging microenvironments affect T cell immunity and explore methods to rejuvenate T cells to combat age-related diseases. | ERC STG | € 1.500.000 | 2023 | Details |
STEM CELL PLASTICITY IN ADULT NEUROGENIC NICHESThis project aims to uncover the molecular mechanisms of plasticity in adult neural stem cells to enhance understanding of their behavior and potential implications for glioma treatment. | ERC ADG | € 2.499.783 | 2023 | Details |
Studying the metabolism and function of myeloid dendritic cells and neutrophils in distinct tissues in health and agingThis project aims to uncover how metabolic adaptations of dendritic cells and neutrophils in various tissues influence their immune functions and dysfunction in aging, paving the way for targeted therapies. | ERC STG | € 1.499.500 | 2024 | Details |
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.
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.
STEM CELL PLASTICITY IN ADULT NEUROGENIC NICHES
This project aims to uncover the molecular mechanisms of plasticity in adult neural stem cells to enhance understanding of their behavior and potential implications for glioma treatment.
Studying the metabolism and function of myeloid dendritic cells and neutrophils in distinct tissues in health and aging
This project aims to uncover how metabolic adaptations of dendritic cells and neutrophils in various tissues influence their immune functions and dysfunction in aging, paving the way for targeted therapies.