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

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

PROVIDER: PRJNA981139 | ENA |

REPOSITORIES: ENA

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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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Single Cell RNA-seq time course of mouse gastruloids at 0h (mESCs), 24h, 48h and 72h post-aggregation

Project description:Single cell transcriptomic study (using 10x Genomics v3 kits) of gastruloids, aggregates of mESCs, at different developmental timepoints (24h, 48h and 72h post-aggregation). mESCs, corresponding to the 0h timepoint, were also sequenced. The aim of this study was to delineate the cell state transition dynamics underlying anteroposterior symmetry breaking and germ layer formation in gastruloids. Gastruloids used in this study were generated from Bra::GFP reporter mESCs (Fehling et al., 2003).

2023-12-04 | E-MTAB-12749 | biostudies-arrayexpress

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Project description:Symmetry breaking in gastruloid development

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Project description:Symmetry breaking in gastruloid development

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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

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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

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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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

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