Summary
Tissue renewal by adult stem cells is regulated by a multitude of cell intrinsic and extrinsic mechanism, 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. However, recent findings by us and others demonstrate that metabolism can actually actively influence cell fate. Moreover, metabolites can be exchanged between neighbor cells in the stem cell niche, raising the question on how cell fate can be accurately controlled.
I hypothesize that 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. 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 daughters cells in the first hours after asymmetric cell division. Second, to assess the extent and impact of metabolite sharing in the stem cell niche, we will develop methods capable of detecting exchange of metabolites that are produced specifically in one cell type and used by others. Finally, to study the impact of niche geometry, we will develop artificial scaffolds instructing custom niche topology, and study the communal metabolism and stem cell fate regulation on tissue mimetic and non-physiologic niche geometries.
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. Moreover, we study two stem cell systems with opposing dynamics, providing insights on general principles and increasing robustness of the study plan. Our work also has the potential to uncover metabolic tools advancing protocols for future cellular therap
I hypothesize that 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. 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 daughters cells in the first hours after asymmetric cell division. Second, to assess the extent and impact of metabolite sharing in the stem cell niche, we will develop methods capable of detecting exchange of metabolites that are produced specifically in one cell type and used by others. Finally, to study the impact of niche geometry, we will develop artificial scaffolds instructing custom niche topology, and study the communal metabolism and stem cell fate regulation on tissue mimetic and non-physiologic niche geometries.
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. Moreover, we study two stem cell systems with opposing dynamics, providing insights on general principles and increasing robustness of the study plan. Our work also has the potential to uncover metabolic tools advancing protocols for future cellular therap
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| Web resources: | https://cordis.europa.eu/project/id/101045009 |
| Start date: | 01-06-2022 |
| End date: | 31-05-2027 |
| Total budget - Public funding: | 2 617 155,00 Euro - 2 617 155,00 Euro |
Cordis data
Original description
Tissue renewal by adult stem cells is regulated by a multitude of cell intrinsic and extrinsic mechanism, 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. However, recent findings by us and others demonstrate that metabolism can actually actively influence cell fate. Moreover, metabolites can be exchanged between neighbor cells in the stem cell niche, raising the question on how cell fate can be accurately controlled.I hypothesize that 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. 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 daughters cells in the first hours after asymmetric cell division. Second, to assess the extent and impact of metabolite sharing in the stem cell niche, we will develop methods capable of detecting exchange of metabolites that are produced specifically in one cell type and used by others. Finally, to study the impact of niche geometry, we will develop artificial scaffolds instructing custom niche topology, and study the communal metabolism and stem cell fate regulation on tissue mimetic and non-physiologic niche geometries.
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. Moreover, we study two stem cell systems with opposing dynamics, providing insights on general principles and increasing robustness of the study plan. Our work also has the potential to uncover metabolic tools advancing protocols for future cellular therap
Status
SIGNEDCall topic
ERC-2021-COGUpdate Date
09-02-2023
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