Summary
Tissue development requires the orchestration of stem cell differentiation and morphogenesis, a process that is conspicuously observed in mammary gland (MG) branching. The MG develops from an embryonic bud of mammary stem cells (MaSCs). Although these stem cells are initially bipotent, giving rise to the outer (basal) and inner (luminal) layers of the adult gland, they become lineage restricted very early in embryogenesis, at around the time of the onset of branching morphogenesis. The timing of lineage restriction coincides with the differential expression of cell polarity and cell adhesion transcripts. Branching morphogenesis then relies on differential cell division, as well as cell rearrangements and migration, but the mechanisms regulating this process in the embryo remain poorly understood.
Based on these observations, we postulate that basal-biased and luminal-biased MaSCs have distinct molecular features during branching morphogenesis. We therefore propose to functionally link the signaling pathways involved in restriction of stem cell potency to the cellular dynamics that ensure branching. To this end, we will characterize the dynamic behaviour of individually labeled MaSCs during the growth of embryonic MG explants and assess their fate, creating a complete fate-behavior map of MG development. Through genetic manipulation, we will probe how cell adhesion, migration, and division impact on lineage specification and tissue growth. Simultaneously, we will skew stem cell differentiation trajectories and assess their influence on cell behavior and organ shape. The outcomes of this project will provide novel insights into the coordinated developmental programs governing stem cell fate and morphogenetic events, both essential to tissue formation. Moreover, they might uncover potential connections to cancer, where differentiatiom and cell polarity play pivotal roles.
Based on these observations, we postulate that basal-biased and luminal-biased MaSCs have distinct molecular features during branching morphogenesis. We therefore propose to functionally link the signaling pathways involved in restriction of stem cell potency to the cellular dynamics that ensure branching. To this end, we will characterize the dynamic behaviour of individually labeled MaSCs during the growth of embryonic MG explants and assess their fate, creating a complete fate-behavior map of MG development. Through genetic manipulation, we will probe how cell adhesion, migration, and division impact on lineage specification and tissue growth. Simultaneously, we will skew stem cell differentiation trajectories and assess their influence on cell behavior and organ shape. The outcomes of this project will provide novel insights into the coordinated developmental programs governing stem cell fate and morphogenetic events, both essential to tissue formation. Moreover, they might uncover potential connections to cancer, where differentiatiom and cell polarity play pivotal roles.
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| Web resources: | https://cordis.europa.eu/project/id/101146540 |
| Start date: | 01-09-2025 |
| End date: | 31-08-2027 |
| Total budget - Public funding: | - 195 914,00 Euro |
Cordis data
Original description
Tissue development requires the orchestration of stem cell differentiation and morphogenesis, a process that is conspicuously observed in mammary gland (MG) branching. The MG develops from an embryonic bud of mammary stem cells (MaSCs). Although these stem cells are initially bipotent, giving rise to the outer (basal) and inner (luminal) layers of the adult gland, they become lineage restricted very early in embryogenesis, at around the time of the onset of branching morphogenesis. The timing of lineage restriction coincides with the differential expression of cell polarity and cell adhesion transcripts. Branching morphogenesis then relies on differential cell division, as well as cell rearrangements and migration, but the mechanisms regulating this process in the embryo remain poorly understood.Based on these observations, we postulate that basal-biased and luminal-biased MaSCs have distinct molecular features during branching morphogenesis. We therefore propose to functionally link the signaling pathways involved in restriction of stem cell potency to the cellular dynamics that ensure branching. To this end, we will characterize the dynamic behaviour of individually labeled MaSCs during the growth of embryonic MG explants and assess their fate, creating a complete fate-behavior map of MG development. Through genetic manipulation, we will probe how cell adhesion, migration, and division impact on lineage specification and tissue growth. Simultaneously, we will skew stem cell differentiation trajectories and assess their influence on cell behavior and organ shape. The outcomes of this project will provide novel insights into the coordinated developmental programs governing stem cell fate and morphogenetic events, both essential to tissue formation. Moreover, they might uncover potential connections to cancer, where differentiatiom and cell polarity play pivotal roles.
Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
22-11-2024
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