RESUMEN
The formation of a central lumen in the human epiblast is a critical step for development. However, because the lumen forms in the epiblast coincident with implantation, the molecular and cellular events of this early lumenogenesis process cannot be studied in vivo. Recent developments using new model systems have revealed insight into the underpinnings of epiblast formation. To provide an up-to-date comprehensive review of human epiblast lumenogenesis, we highlight recent findings from human and mouse models with an emphasis on new molecular understanding of a newly described apicosome compartment, a novel 'formative' state of pluripotency that coordinates with epiblast polarization, and new evidence about the physical and polarized trafficking mechanisms contributing to lumenogenesis.
Asunto(s)
Quistes , Estratos Germinativos , Animales , Diferenciación Celular , Humanos , RatonesRESUMEN
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.