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Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids [mRNASeq]

ABSTRACT: We report the effect of Budesonode on embryonic stem-to-mesenchymal-like transition (esMT) and 3D Gastruloids

ORGANISM(S): Mus musculus

PROVIDER: GSE199765 | GEO | 2022/09/23

REPOSITORIES: GEO

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Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids [mRNASeq3prime]

Project description:We report the effect of Budesonode on embryonic stem-to-mesenchymal-like transition (esMT) and 3D Gastruloids

2022-09-23 | GSE199766 | GEO

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids.

Project description:3D embryonic stem cell (ESC) aggregates self-organize into embryo-like structures named gastruloids that recapitulate the axial organization of post-implantation embryos. Crucial in this process is the symmetry-breaking event that leads to the emergence of asymmetry and spatially ordered structures from homogeneous cell aggregates. Here, we show that budesonide, a glucocorticoid drug widely used to treat asthma, prevents ESC aggregates to break symmetry. Mechanistically, the effect of budesonide is glucocorticoid receptor independent. RNA sequencing and lineage fate analysis reveal that budesonide counteracts exit from pluripotency and modifies the expression of a large set of genes associated with cell migration, A-P axis formation, and WNT signaling. This correlates with reduced phenotypic and molecular cell heterogeneity, persistence of E-CADHERIN at the cell-cell interface, and cell aggregate compaction. Our findings reveal that cell-cell adhesion properties control symmetry breaking and cell fate transition in 3D gastruloids and suggest a potential adverse effect of budesonide on embryo development.

| S-EPMC9669408 | biostudies-literature

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-23 | GSE199767 | GEO

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids [mRNASeq]

Project description:Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids [mRNASeq]

| PRJNA821474 | ENA

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

Project description:Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids

| PRJNA821461 | ENA

Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids [mRNASeq3prime]

Project description:Stabilization of cell-cell adhesions prevents symmetry breaking and locks in pluripotency in 3D gastruloids [mRNASeq3prime]

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Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids

Project description:Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. As metabolism can control cell growth while also providing mechanistic links to developmental signalling pathways, it is ideally placed to enable this coordination. To understand how metabolism impacts early mesoderm specification, we used mouse embryonic stem (ES) cell-derived gastruloids, as these enable temporal control over metabolic manipulations and can be generated in large quantities. Gastruloids show mosaic expression of two glucose transporters,Slc2a1andSlc2a3both of which co-express with the expression of both the mesodermal markerT/Braand the neural markerSox2. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG specifically blocks the expression ofT/Brawithout affecting the expression ofSox2and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. Together, our results show that while mannose is crucial for mesoderm specification, the glycolytic pathway is dispensable at early stages ofT/Braexpression in gastruloids.

2024-03-11 | GSE236887 | GEO

Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids

Project description:Patterning and growth are fundamental features of embryonic development that must be tightly coordinated during morphogenesis. While metabolism is known to control cell growth, how it impacts patterning and links to morphogenesis is poorly understood. To understand how metabolism impacts early mesoderm specification during gastrulation, we used in vitro mouse embryonic stem (ES) cell-derived gastruloids, due to ease of metabolic manipulations and high-throughput nature. Gastruloids showed mosaic expression of glucose transporters co-expressing with the mesodermal marker T/Bra. To understand the significance of cellular glucose uptake in development, we used the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG). 2-DG blocked the expression of T/Bra and abolishes axial elongation in gastruloids. Surprisingly, removing glucose completely from the medium did not phenocopy 2-DG treatment despite a significant decline in glycolytic intermediates occurring under both conditions. As 2-DG can also act as a competitive inhibitor of mannose in protein glycosylation, we added mannose together with 2-DG and found that it could rescue the mesoderm specification. We corroborated these results in vivomouse embryos where supplementing mannose rescued the 2-DG mediated phenotype of mesoderm specification and proximo-distal elongation of the primitive streak. We further showed that blocking production and intracellular recycling of mannose abrogated mesoderm specification. At molecular level, proteomics analysis revealed that mannose reversed glycosylation of the Wnt pathway regulator, Secreted Frizzled Receptor, Frzb, expressed in the primitive streak of the mouse embryo. Our study showed how mannose linked metabolism to glycosylation of a developmental pathway component, crucial in patterning of mesoderm and morphogenesis of gastruloids.

2024-01-12 | MSV000093849 | MassIVE

Symmetry breaking and germ layer emergence through optogenetic Wnt activation in gastruloids

Project description:Human gastrulation is a dynamic, complex, and poorly understood process. Starting from a seemingly homogenous population, cell and tissue organization during this process establishes the 3D organismal body plan. However, due to technical and ethical limitations, mechanisms of human gastrulation are largely unexplored. For example, it is generally unclear whether a spatially ordered, external cue is necessary for patterning, or whether the epiblast harbors the innate ability to differentiate and self-organize in the absence of asymmetric cues. Human pluripotent stem cells (hPSCs) fortunately offer the potential to model gastrulation, most notably through generation of 3D “gastruloids”. Here we use optogenetic control of Wnt signaling to establish a 3D hPSC gastruloid model and demonstrate the spatially-ordered emergence of the three germ layer lineages in the absence of exogenous asymmetrical cues.

2024-06-03 | GSE234371 | GEO

Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids

Project description:Mannose is crucial for mesoderm specification and symmetry breaking in gastruloids

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