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Spatiotemporal lineage derepression by cell crowding-induced ETV4 inactivation

GSE183702 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/03/12 Platform GPL24676
Summary
All extant amniotes employ a single-layered epithelium of epiblasts as a starting material for gastrulation, suggesting the necessity of the epithelial structure for three germ layer derivation. Using a human embryonic stem cell (hESC) epithelium as a model system, we found that local epithelial crowding derepresses the neuroectoderm fate by spatiotemporal inactivation of ETV4. ETV4 serves as a genetic toggle switch that links cell density to lineage fates. Mechanistically, cell crowding blocks FGF receptor endocytosis by reduced cell-extracellular matrix (ECM) interaction. Disrupted endocytosis decreases ETV4 protein stability by ERK inactivation. Mathematical modeling of epithelial crowding demonstrates that the cooperativity of integrin-ECM interaction transforms the gradient of crowdedness into bistable ETV4 transition, which ensures the switch-like function of ETV4 in lineage determination. Our results propose local cell crowding in a stem cell epithelium as a key cellular mechanism for spatiotemporal regulation of lineage fates.
Published in
ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification
Yang S, Golkaram M, Oh S et al. · Nature cell biology 2024 · PMID 38702503 · doi:10.1038/s41556-024-01415-w
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Also filed as BioProject PRJNA761710 and SRA study SRP336205. Searching any of these in the dataset finder brings you back here.

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