SubsidieMeestersNiche geometry as the regulator of communal metabolism and cell fate
This project aims to investigate how communal metabolism and niche geometry influence stem cell fate decisions through metabolic pathways and metabolite sharing in tissue renewal.
Projectdetails
Introduction
Tissue renewal by adult stem cells is regulated by a multitude of cell intrinsic and extrinsic mechanisms, which jointly guide decisions between stem cell self-renewal and differentiation. Change between these two cellular fates is considered to result from transcriptional events that sequentially alter the function of the whole cell – including its metabolism.
Metabolic Influence on Cell Fate
However, recent findings by us and others demonstrate that metabolism can actually actively influence cell fate. Moreover, metabolites can be exchanged between neighboring cells in the stem cell niche, raising the question of how cell fate can be accurately controlled.
Hypothesis
I hypothesize that the fate of tissue stem cells is controlled by metabolism running jointly within the surrounding cellular community, and the geometry of the niche regulates stem cells via effects on this communal metabolism.
Research Objectives
In order to first identify metabolic pathways capable of altering cell fate, we will:
- Establish the exact order of metabolic and transcriptional events that distinguish the two daughter cells in the first hours after asymmetric cell division.
- Assess the extent and impact of metabolite sharing in the stem cell niche by developing methods capable of detecting the exchange of metabolites that are produced specifically in one cell type and used by others.
- Study the impact of niche geometry by developing artificial scaffolds instructing custom niche topology, and investigate the communal metabolism and stem cell fate regulation on tissue mimetic and non-physiologic niche geometries.
Research Tools
The work is enabled by our unique research tools allowing identification of cells with distinct fates based on the chronological age of organelles they inherit in cell division.
Stem Cell Systems
Moreover, we study two stem cell systems with opposing dynamics, providing insights on general principles and increasing the robustness of the study plan.
Potential Impact
Our work also has the potential to uncover metabolic tools advancing protocols for future cellular therapy.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.617.155 |
| Totale projectbegroting | € 2.617.155 |
Tijdlijn
| Startdatum | 1-6-2022 |
| Einddatum | 31-5-2027 |
| Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- HELSINGIN YLIOPISTOpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
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 |
Spatial and temporal regulation of cell competitionThis project aims to unravel the spatial and temporal regulation of cell competition and its effects on tissue composition and tumor growth using an innovative 3D co-culture system and advanced imaging techniques. | ERC Consolid... | € 1.999.993 | 2025 | Details |
Collective Regulation of Cell DecisionsThis project aims to explore how collective tissue properties influence cell decisions in zebrafish by manipulating cell parameters to engineer tissue characteristics and uncover developmental mechanisms. | ERC Starting... | € 2.486.429 | 2025 | 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 |
Uncovering the Diversity of Cell-Cell Interactions that Impact Cell FatesThis project aims to develop a novel method for high-resolution transcriptomic analysis of cellular microenvironments to understand how cell communication influences neural crest cell development and fate. | ERC Starting... | € 1.499.900 | 2023 | Details |
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.
Spatial and temporal regulation of cell competition
This project aims to unravel the spatial and temporal regulation of cell competition and its effects on tissue composition and tumor growth using an innovative 3D co-culture system and advanced imaging techniques.
Collective Regulation of Cell Decisions
This project aims to explore how collective tissue properties influence cell decisions in zebrafish by manipulating cell parameters to engineer tissue characteristics and uncover developmental mechanisms.
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.
Uncovering the Diversity of Cell-Cell Interactions that Impact Cell Fates
This project aims to develop a novel method for high-resolution transcriptomic analysis of cellular microenvironments to understand how cell communication influences neural crest cell development and fate.