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Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [scRNA-seq]

ABSTRACT: Mouse extended pluripotent stem (EPS) cells have demonstrated significant potential for generating embryo models in vitro. However, their limited capacity for extraembryonic trophoblast development has hindered their use in constructing whole embryo models, particularly post-implantation embryoids. Here, we establish a stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells. These cells retain trophectoderm-specific transcriptomic features and can differentiate into trophoblast lineages in vivo. Moreover, combining these trophectoderm-like cells with EPS cell-derived primitive endoderm/epiblast bilineage structures enabled the robust generation of post-implantation embryoids in a transgene-free manner. EPS-derived embryoids recapitulate key developmental events of post-implantation mouse embryos, including the formation of the pro-amniotic cavity, anterior-posterior axis, primitive streak, gastrulation, and complex extraembryonic tissues. Notably, single-cell transcriptomic analysis revealed a high degree of transcriptional similarity between EPS-derived embryoids at day 6 and natural E7.5 mouse embryos. Our study presents a novel platform for modeling post-implantation mouse embryogenesis in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE291069 | GEO | 2025/10/21

REPOSITORIES: GEO

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Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [bulk RNA-seq]

Project description:Mouse extended pluripotent stem (EPS) cells have demonstrated significant potential for generating embryo models in vitro. However, their limited capacity for extraembryonic trophoblast development has hindered their use in constructing whole embryo models, particularly post-implantation embryoids. Here, we establish a stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells. These cells retain trophectoderm-specific transcriptomic features and can differentiate into trophoblast lineages in vivo. Moreover, combining these trophectoderm-like cells with EPS cell-derived primitive endoderm/epiblast bilineage structures enabled the robust generation of post-implantation embryoids in a transgene-free manner. EPS-derived embryoids recapitulate key developmental events of post-implantation mouse embryos, including the formation of the pro-amniotic cavity, anterior-posterior axis, primitive streak, gastrulation, and complex extraembryonic tissues. Notably, single-cell transcriptomic analysis revealed a high degree of transcriptional similarity between EPS-derived embryoids at day 6 and natural E7.5 mouse embryos. Our study presents a novel platform for modeling post-implantation mouse embryogenesis in vitro.

2025-10-21 | GSE291068 | GEO

RNA-seq of XTE cells and vesicles, XEN and XEN-like cells, and ES cells

Project description:The conventional trophoblast stem cells represent post-implantation extraembryonic ectoderm-like state and not that of pre-implantation trophectoderm, irrespective of their origin. To capture the trophectoderm-like state we established culture conditions that facilitate the co-existence of characteristics of both the extraembryonic lineages, namely, primitive endoderm and trophectoderm. We term these cells XTE cells. We carried out RNA-seq on XTE cells from different origins, as well as XEN cells, XEN-like cells, and ES cells, to assess their transcriptional profiles and identify putative marker genes and master regulators.

2022-09-13 | E-MTAB-8788 | biostudies-arrayexpress

Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [scRNA-seq]

Project description:Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [scRNA-seq]

| PRJNA1231500 | ENA

Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [bulk RNA-seq]

Project description:Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [bulk RNA-seq]

| PRJNA1231499 | ENA

XEN state reprogramming into self-organizing trophectoderm-like cells enables the assembly of synthetic embryoids

Project description:We established culture conditions that enable the two fates of blastocysts’ extraembryonic lineages – the primitive endoderm and the trophectoderm – to co-exist in a shared XTE state. The XTE cells exhibit robust self-organization capacity and in combination with ES cells enable the assembly of blastocyst-like embryoids.

2022-09-13 | GSE159883 | GEO

Single-cell RNA-seq reveals sequential trophoblast transition during human embryo implantation

Project description:We performed single-cell RNA sequencing (scRNA-seq) analysis of human post-implantation trophoblast cells. A hierarchical model was established, which was characterized by the sequential and stepwise development of two primitive cytotrophoblast cell (pCTB) subtypes after the trophectoderm (TE), two primitive syncytiotrophoblast (pSTB) subtypes, and migrative trophoblast cells (MTB). Further analysis characterized a new subtype of fusion-competent cells, which not only prepare for fusion to form primitive syncytiotrophoblast but also possess migration ability, which could be dual-function cells during implantation. Our work allows for reconstruction of sequential trophoblast cell transcriptional programs transition during implantation and provides a valuable resource to study pathologies in early pregnancy, such as recurrent implantation failure.

2022-07-07 | GSE156456 | GEO

Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential

Project description:Classical mouse embryology has established a paradigm of early development drivenby sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derivedfrom early epiblast have lost the potency to produce extraembryonic trophectoderm.We show in contrast that human naive epiblast cells readily make trophectoderm.Inhibition of ERK signalling, instrumental in naive stem cell propagation, unexpectedlypotentiates trophectoderm formation, an effect enhanced by Nodal inhibition.Transcriptome analyses authenticate conversion into trophectoderm with subsequentproduction of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Geneticperturbations indicate that NANOG suppresses and TFAP2C enables trophectoderminduction. Consistent with post-implantation progression, trophectoderm potential isextinguished in conventional human pluripotent stem cells, which instead makeamnion. Finally, human embryo epiblasts from late blastocysts efficiently generatetrophectoderm and differentiated trophoblast. Thus, pluripotent cells in the humanembryo retain extraembryonic lineage plasticity and regenerative potential untilimplantation. Harnessing this unanticipated regulative capacity may be beneficial forassisted reproduction technology.

2021-02-10 | GSE166422 | GEO

Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential

2021-02-09 | GSE166401 | GEO

De novo formation of apical-basal polarity by Rap1 regulates epiblast patterning

Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.

2022-06-14 | PXD028315 | Pride

Stem cell lines of the early mouse embryo

Project description:Expression profiling of stem cell lines derived from the early embryo representing the trophoblast, primitive endoderm, early epiblast (inner cell mass E3.5) and late post-implantation epiblast (E5.5). Cells were grown without feeders and harvested. Comparisons were made to provide evidence of unique gene expression between the cell lines. Specifically, pre-implantation (ICM, epiblast and primitive endoderm, and trophoblast), as well as pre-implantation and post-implantation epiblasts.

2012-05-21 | E-GEOD-34799 | biostudies-arrayexpress

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