SubsidieMeestersStem 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.
Projectdetails
Introduction
Coherent tissue growth and repair require an interplay between stem cells and their local and systemic environment. The dynamics of this process remain poorly defined, particularly at the intersection with disease. Cellular quiescence is adopted by many adult stem cells, conferring them several features including a smaller cell volume and reduced metabolic demand. This suggests that quiescence preserves stem cell properties, making them less responsive to external cues.
Research Focus
We examined the status of skeletal muscle stem (MuSC) and niche cells during an influenza virus infection (lung) and cancer cachexia (tumor) in mice. Unexpectedly, quiescent MuSCs remodeled their cellular, metabolic, and transcriptome properties extensively, and tissue regeneration was impaired. This prompted us to define a novel cell state, GPath. Whether GPath represents a coordinated response of stem cells to pathology or uncontrolled deregulation is unclear.
Observations
MuSCs exhibit remarkable diversity in gene regulation and function in distinct anatomical locations (head/limb). We discovered that cranial MuSCs display higher resistance to the pathologies compared to those in the limb. These observations have led us into a novel area of research, which, to the best of my knowledge, is largely unexplored in model organisms and humans:
- How stem and niche cells in one organ respond to pathologies present at a distal site.
Methodology
We will examine the response of muscle and blood stem and niche cells to distal pathologies by defining their cellular, metabolic, molecular, epigenetic, and functional properties, as well as their modes of cell division.
Approaches
We will employ diverse multiomics approaches and novel medium/high-throughput intravital and ex vivo imaging pipelines. This work should provide new knowledge and tools to address an important, but under-investigated area of research where stem cell biology and pathologies converge.
Implications
The knowledge gained will be widely applicable to other stem cell systems and will inform on human pathologies.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.499.600 |
| Totale projectbegroting | € 2.499.600 |
Tijdlijn
| Startdatum | 1-9-2022 |
| Einddatum | 31-8-2027 |
| Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- INSTITUT PASTEURpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
The Interplay of Aging, Immune Signaling and Stem Cell FunctionThis 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. | ERC Consolid... | € 1.998.843 | 2024 | Details |
Mutations in healthy tissues: a double-edged sword for tissues homeostasisThis 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. | ERC Synergy ... | € 9.808.142 | 2025 | Details |
PErPetuating Stemness: From single-cell analysis to mechanistic spatio-temporal models of neural stem cell dynamicsThis project aims to decode the mechanisms of neural stem cell heterogeneity and behavior through experimental and mathematical approaches, enhancing understanding and manipulation of stemness. | ERC Synergy ... | € 10.858.174 | 2023 | Details |
Metabolic regulation of the skeletal stem cell nicheThis project aims to investigate the role of a novel niche cell type in skeletal stem cell maintenance and its metabolic regulation using zebrafish, to inform therapies for metabolic diseases and skeletal health. | ERC Starting... | € 1.499.821 | 2024 | 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 Advanced... | € 2.499.783 | 2023 | Details |
The 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.
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.
PErPetuating Stemness: From single-cell analysis to mechanistic spatio-temporal models of neural stem cell dynamics
This project aims to decode the mechanisms of neural stem cell heterogeneity and behavior through experimental and mathematical approaches, enhancing understanding and manipulation of stemness.
Metabolic regulation of the skeletal stem cell niche
This project aims to investigate the role of a novel niche cell type in skeletal stem cell maintenance and its metabolic regulation using zebrafish, to inform therapies for metabolic diseases and skeletal health.
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.