Lumen expansion is initially driven by apical actin polymerization followed by osmotic pressure in a human epiblast model.
Cell Stem Cell
; 31(5): 640-656.e8, 2024 May 02.
Article
en En
| MEDLINE
| ID: mdl-38701758
ABSTRACT
Post-implantation, the pluripotent epiblast in a human embryo forms a central lumen, paving the way for gastrulation. Osmotic pressure gradients are considered the drivers of lumen expansion across development, but their role in human epiblasts is unknown. Here, we study lumenogenesis in a pluripotent-stem-cell-based epiblast model using engineered hydrogels. We find that leaky junctions prevent osmotic pressure gradients in early epiblasts and, instead, forces from apical actin polymerization drive lumen expansion. Once the lumen reaches a radius of â¼12 µm, tight junctions mature, and osmotic pressure gradients develop to drive further growth. Computational modeling indicates that apical actin polymerization into a stiff network mediates initial lumen expansion and predicts a transition to pressure-driven growth in larger epiblasts to avoid buckling. Human epiblasts show transcriptional signatures consistent with these mechanisms. Thus, actin polymerization drives lumen expansion in the human epiblast and may serve as a general mechanism of early lumenogenesis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Presión Osmótica
/
Actinas
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Polimerizacion
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Estratos Germinativos
Límite:
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article