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| Status |
Public on Mar 12, 2024 |
| Title |
Spatiotemporal lineage derepression by cell crowding-induced ETV4 inactivation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| 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.
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| |
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| Overall design |
mRNA profiles of ETV4 +/- and low/high density H9 hESCs.
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| |
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| Contributor(s) |
Yang S, Jang J |
| Citation(s) |
38702503 |
| |
| Submission date |
Sep 08, 2021 |
| Last update date |
Jun 12, 2024 |
| Contact name |
Seungbok Yang |
| Organization name |
POSTECH
|
| Lab |
PSCB
|
| Street address |
47, Jigok-ro
|
| City |
Pohang-si |
| ZIP/Postal code |
37666 |
| Country |
South Korea |
| |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA761710 |
| SRA |
SRP336205 |
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