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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE106227 | GEO | 2018/06/01

REPOSITORIES: GEO

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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

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

Project description:Gastruloids are 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). We analyzed the transcriptomic profiles of gastruloids at different time-points after aggregation (AA), showing that they are capable of organizing a post-occipital pattern of neural, mesodermal and endodermal derivatives that mimics that of the embryo in terms of gene expression.

2018-06-01 | GSE106225 | GEO

Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids [E6.5 to E9.5]

Project description:Gastruloids are 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). We analyzed the transcriptomic profiles of gastruloids at different time-points after aggregation (AA) and compared them with those of mouse embryo at different stages, raging from e6 to e9.5. We show that gastruloids are capable of organizing a post-occipital pattern of neural, mesodermal and endodermal derivatives that mimics that of the embryo in terms of gene expression.

2018-06-01 | GSE113885 | GEO

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

Project description:Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids

| PRJNA415967 | ENA

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

Project description:Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids [bulk]

| PRJNA416036 | ENA

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

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

| PRJNA415971 | ENA

Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids [E6.5 to E9.5]

Project description:Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids [E6.5 to E9.5]

| PRJNA454332 | ENA

Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells.

Project description:Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call 'gastruloids'.

| S-EPMC4302915 | biostudies-literature

Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids.

Project description:Human embryonic stem cells cultured in 2D micropatterns with BMP4 differentiate into a radial arrangement of germ layers and extraembryonic cells. Single-cell transcriptomes demonstrate generation of cell types transcriptionally similar to their in vivo counterparts in Carnegie stage 7 human gastrula. Time-course analyses indicate sequential differentiation, where the epiblast arises by 12 h between the prospective ectoderm in the center and the cells initiating differentiation toward extraembryonic fates at the edge. Extraembryonic and mesendoderm precursors arise from the epiblast by 24 h, while nascent mesoderm, endoderm, and primordial germ cell-like cells form by 44 h. Dynamic changes in transcripts encoding signaling components support a BMP, WNT, and Nodal hierarchy underlying germ-layer specification conserved across mammals, and FGF and HIPPO pathways being active throughout differentiation. This work also provides a resource for mining genes and pathways expressed in a stereotyped 2D gastruloid model, common with other species or unique to human gastrulation.

| S-EPMC8185470 | biostudies-literature

Mouse embryonic stem cells with a multi-integrase mouse artificial chromosome for transchromosomic mouse generation.

Project description:The mouse artificial chromosome (MAC) has several advantages as a gene delivery vector, including stable episomal maintenance of the exogenous genetic material and the ability to carry large and/or multiple gene inserts including their regulatory elements. Previously, a MAC containing multi-integration site (MI-MAC) was generated to facilitate transfer of multiple genes into desired cells. To generate transchromosomic (Tc) mice containing a MI-MAC with genes of interest, the desired genes were inserted into MI-MAC in CHO cells, and then the MI-MAC was transferred to mouse embryonic stem (mES) cells via microcell-mediated chromosome transfer (MMCT). However, the efficiency of MMCT from CHO to mES cells is very low (<10(-6)). In this study, we constructed mES cell lines containing a MI-MAC vector to directly insert a gene of interest into the MI-MAC in mES cells via a simple transfection method for Tc mouse generation. The recombination rate of the GFP gene at each attachment site (FRT, PhiC31attP, R4attP, TP901-1attP and Bxb1attP) on MI-MAC was greater than 50% in MI-MAC mES cells. Chimeric mice with high coat colour chimerism were generated from the MI-MAC mES cell lines and germline transmission from the chimera was observed. As an example for the generation of Tc mice with a desired gene by the MI-MAC mES approach, a Tc mouse strain ubiquitously expressing Emerald luciferase was efficiently established. Thus, the findings suggest that this new Tc strategy employing mES cells and a MI-MAC vector is efficient and useful for animal transgenesis.

| S-EPMC4504986 | biostudies-literature

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