Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multimodal characterization of murine gastruloid development

ABSTRACT: Gastruloids are highly scalable, three-dimensional assemblies generated from pluripotent stem cells that recapitulate fundamental principles of embryonic pattern formation in vitro. Using single cell RNA and multiome sequencing we provide a comprehensive resource mapping cellular states and cell types found during gastruloid development and compare them to the in vivo embryo. We further develop a high throughput gastruloid handling and imaging pipeline to spatially monitor cell type emergence and unfolding of symmetry breaking during gastruloid development. We report spatial variability of pluripotency states in early gastruloids that determines a binary cell response to Wnt activation. While cells situated in the core of the gastruloid revert to an ectopic pluripotent state, peripheral cells differentiate to a primitive streak like state. These two populations then cause gastruloids to break radial symmetry, allowing axial elongation and commitment to the three embryonic germ layers. Finally by performing a phenotypic compound screen, we perturb thousands of gastruloids at relevant developmental time points deriving a phenotypic landscape and inferring molecular regulator networks underlying gastruloid development. Employing this resource, we improve the formation of anterior structures in the existing gastruloid model, using a dual Wnt modulation approach to differentiate an anterior ectopic pluripotent core to anterior ecto- and endodermal structures. This work gives is a resource to understand how gastruloids develop and, more generally, how homogenous cell populations can generate complex patterns in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE229386 | GEO | 2023/09/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gastruloids generated without exogenous Wnt activation develop anterior neural tissues [EmbryoidsTruseq2]

Project description:Here we describe an approach to generate gastruloids that have a more complete antero-posterior development. We used bioengineered hydrogel microwell arrays to promote the robust derivation of mouse ESCs into post-implantation epiblast-like (EPI) aggregates in a reproducible and scalable manner. These EPI aggregates break symmetry and axially elongate without external chemical stimulation. Inhibition of WNT signaling in early stages of development leads to the formation of gastruloids with anterior neural tissues.

2021-04-12 | GSE171210 | GEO

Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids [individual]

Project description:Gastruloids, small aggregates of murine Embryonic Stem (ES) cells stimulated to undergo gastrulation-like symmetry breaking events in vitro (van den Brink, S. C. et al. 2014, Simunovic, M. & Brivanlou, A. H 2017). Analysis of the transcriptional profiles from pools of gastruloids collected at different time-points after aggregation (AA) revealed that gastruloids are capable of organizing an axially integrated post-occipital pattern of neural, mesodermal and endodermal derivatives that mimics that of the embryo in terms of gene expression. To test the homogeneity and reproducibility of the transcriptional programs uncovered by our bulked RNAseq experiments, we performed RNAseq analysis of individual gastruloids collected at different time-points AA (10 biological replicates per time-point). Our results indicates that the transcriptional profiles of gastruloid were highly reproducible at each time points and that each gastruloid implement the full diversity of transcriptional programs detected in our bulked RNAseq experiments.

2018-06-01 | GSE106226 | GEO

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

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

Recapitulating human peri-gastrulation development via self-organization of extended pluripotent stem cells

Project description:Stem cell models that replicate the gastrulation process in human embryos have been created, but they lack the essential extraembryonic cells needed for early embryonic development and patterning. Here, we introduce a robust and efficient method that prompts human extended pluripotent stem (EPS) cells to self-organize into embryo-like structures, called peri-gastruloids, which encompass both embryonic (epiblast) and extraembryonic (hypoblast) tissues. These peri-gastruloids simulate critical stages of human peri-gastrulation development, such as forming amniotic and yolk sac cavities, developing bilaminar and trilaminar embryonic discs, specifying primordial germ cells, initiating gastrulation, and early neurulation. Single-cell RNA sequencing unveiled transcriptomic characteristics of these human peri-gastruloids, which closely resemble the primary peri-gastrulation cell types found in human and non-human primates. Our results emphasize the remarkable self-organizing ability of EPS cells to generate advanced human embryo-like structures. This peri-gastruloid platform allows for further exploration beyond gastrulation and may potentially aid in the development of human fetal tissues for use in regenerative medicine.

2023-07-20 | GSE232861 | GEO

Symmetry breaking in gastruloid development

Project description:Symmetry breaking in gastruloid development

| PRJNA759809 | ENA

Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids

Project description:The cellular microenvironment together with intrinsic regulators shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and appear to benefit from hypoxic culture in vitro. Yet, how hypoxia influences stem cell transcriptional networks and lineage choices remain poorly understood. Here we investigated the molecular effects of acute and prolonged hypoxia on embryonic and extraembryonic stem cells as well as the functional impact on differentiation potential. We find a temporal and cell type-specific transcriptional response including an early primitive streak signature in hypoxic embryonic stem cells (ESCs) mediated by HIF1. Using a 3D gastruloid differentiation model, we show that hypoxia-induced T expression enables symmetry breaking and axial elongation in the absence of exogenous WNT activation. When combined with exogenous WNT activation, hypoxia enhances lineage representation in gastruloids, as demonstrated by highly enriched signatures of gut endoderm, notochord, neuromesodermal progenitors and somites. Our findings directly link the microenvironment to stem cell function and provide a rationale supportive of applying physiological conditions in models of embryo development.

2022-08-24 | GSE178628 | GEO

Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids [RNA-seq]

2022-08-24 | GSE178624 | GEO

Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids

2022-08-24 | GSE195545 | GEO

Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids

2022-08-24 | GSE195544 | GEO