Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst [mouse_ERKi_scRNAseq]

ABSTRACT: Studies in the mouse demonstrate the importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) in specification of embryo-fated epiblast and yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) cells prior to implantation. Molecular mechanisms regulating specification of early lineages in human development are comparatively unclear. Here we show that exogenous FGF stimulation leads to expanded hypoblast molecular marker expression, at the expense of the epiblast. Conversely, we show that specifically inhibiting ERK activity leads to expansion of epiblast cells functionally capable of giving rise to naïve human pluripotent stem cells. Single-cell transcriptomic analysis indicates that these epiblast cells downregulate FGF signalling and maintain molecular markers of the epiblast. Our functional study demonstrates the molecular mechanisms governing ICM specification in human development, whereby segregation of the epiblast and hypoblast lineages occurs during maturation of the mammalian embryo in an ERK signal-dependent manner.

ORGANISM(S): Mus musculus

PROVIDER: GSE297478 | GEO | 2025/06/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst

Project description:Studies in the mouse demonstrate the importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) in specification of embryo-fated epiblast and yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) cells prior to implantation. Molecular mechanisms regulating specification of early lineages in human development are comparatively unclear. Here we show that exogenous FGF stimulation leads to expanded hypoblast molecular marker expression, at the expense of the epiblast. Conversely, we show that specifically inhibiting ERK activity leads to expansion of epiblast cells functionally capable of giving rise to naïve human pluripotent stem cells. Single-cell transcriptomic analysis indicates that these epiblast cells downregulate FGF signalling and maintain molecular markers of the epiblast. Our functional study demonstrates the molecular mechanisms governing ICM specification in human development, whereby segregation of the epiblast and hypoblast lineages occurs during maturation of the mammalian embryo in an ERK signal-dependent manner.

2025-06-11 | GSE297052 | GEO

Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst [RNA-seq II]

Project description:Studies in the mouse demonstrate the importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) in specification of embryo-fated epiblast and yolk-sac-fated hypoblast cells from uncommitted inner cell mass (ICM) cells prior to implantation. Molecular mechanisms regulating specification of early lineages in human development are comparatively unclear. Here we show that exogenous FGF stimulation leads to expanded hypoblast molecular marker expression, at the expense of the epiblast. Conversely, we show that specifically inhibiting ERK activity leads to expansion of epiblast cells functionally capable of giving rise to naive human pluripotent stem cells. Single-cell transcriptomic analysis indicates that these epiblast cells downregulate FGF signalling and maintain molecular markers of the epiblast. Our functional study demonstrates the molecular mechanisms governing ICM specification in human development, whereby segregation of the epiblast and hypoblast lineages occurs during maturation of the mammalian embryo in an ERK signal-dependent manner.

2025-06-11 | GSE250613 | GEO

Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst [RNA-seq I]

Project description:Studies in the mouse demonstrate the importance of fibroblast growth factor (FGF) and extra-cellular receptor tyrosine kinase (ERK) in specification of the epiblast and hypoblast in the inner cell mass (ICM). We recently demonstrated cross-talk of ERK and PI3K activity downstream of FGF and insulin growth factor signaling. We therefore hypothesized that ERK may have a conserved role in human hypoblast versus epiblast specification. Here we determined that FGF signaling is sufficient to specify hypoblast in human blastocysts. We describe ERK signaling during the blastocyst stage and demonstrate that blocking ERK activity, by small-molecule inhibition, is necessary for hypoblast specification in human blastocysts, and leads to expansion of the epiblast cells functionally capable of giving rise to naïve pluripotent embryonic stem cells. Transcriptomic analysis further reveals that these epiblast cells downregulate insulin growth factor and FGF signaling, while maintaining molecular markers of the epiblast. Moreover, we generate human naïve pluripotent stem cells following ERK inhibition. Our functional studies provide mechanistic insight into human blastocyst formation. We propose a unified model in which segregation of the epiblast and hypoblast lineages occurs during maturation of the mammalian blastocyst in an FGF/ERK signal-dependent manner.

2025-06-11 | GSE239843 | GEO

PI3K/AKT signalling regulates mouse Inner Cell Mass (ICM) progenitor specification [scRNA-seq]

Project description:The inner cell mass (ICM) of early mouse embryos is specified into Epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA6 in combination with FGF/ERK signaling are central actors in ICM fate choice. However, what initiates the specification of the bipotent ICM progenitor and whether other factors are involved in this process is not fully understood yet. Here, we report the key role of PI3K in mouse ICM progenitors specification. Surprisingly, while the PI3K/AKT signaling pathway is known for almost two decades to participate to the maintenance of pluripotency in stem cells, no role for this pathway in ICM cell fate decisions has been reported so far. This is likely due to the dynamic and asynchronous nature of ICM specification combined with the pleiotropic and rapidly evolving functions mediated by PI3K/AKT. By limiting the perturbations of the pathway to a short time-window corresponding to the early phase of ICM specification, we unravelled a dual role of PI3K in ICM progenitor, being required on the one hand for the maintenance of pluripotency TFs and, on the other hand, for the competence to engage into PrE differentiation in response to FGF signaling. Thus, our work identifies PI3K as a novel critical regulator of ICM progenitor specification in the mouse embryo.

2024-10-25 | GSE234578 | GEO

PI3K/AKT signalling regulates mouse Inner Cell Mass (ICM) progenitor specification [FLASH-seq]

2024-10-25 | GSE265767 | GEO

Cell-to-cell gene expression variability followed by reinforcement progressively segregates lineages in the early mouse embryo

Project description:Mammalian embryonic development begins with the specification and segregation of the two extra-embryonic lineages, trophectoderm and primitive endoderm, from the pluripotent embryonic lineage, the epiblast. To establish a map of epiblast (EPI) versus primitive endoderm (PrE) lineage segregation which occurs within the inner cell mass (ICM), we comprehensively characterised the gene expression profiles of individual inner cells during blastocyst development. Lineage represents the two embryonic cell lineages: the epiblast (EPI), and the primitive endoderm (PE), which are segregated within the inner cell mass(ICM) during blastocyst development.

2013-11-26 | E-MTAB-1681 | biostudies-arrayexpress

Preimplantation mouse embryo proteome during 8C to 16C division

Project description:Preimplantation stages of mouse embryo development involve temporal and spatial specification and segregation of three late blastocyst cell lineages; trophectoderm (TE), primitive endoderm (PrE) and epiblast (EPI). Spatial separation of the outer TE lineage from the two inner-cell-mass (ICM) lineages (PrE and EPI) starts with the 8- to 16-cell transition and concludes following transit through the 16- to 32-cell stages. This results in a nascent early blastocyst ICM derived from descendants of primary founding inner cells and a secondarily contributed population; of which subsequent relative EPI versus PrE potencies are subject to debate. We showed that generation of primary but not the secondary ICM populations is highly dependent on temporally discreet activation of the mammalian target of rapamycin (mTOR – specifically mTORC1) around 8-cell stage M-phase entry. Moreover, that this role is mediated via the regulated function of the 7-methylguanosine- (7mG) cap binding initiation complex (EIF4F) and potentiating the translation of a subset of key but otherwise intransigent mRNAs containing 5’ UTR terminal oligopyrimidine (TOP-) sequence motifs. To find out translation of which mRNAs is regulated by mTOR during 8- to 16-cell transition, we analysed proteomes of control and mTOR-inhibited embryos during this time window.

2023-08-18 | PXD039423 | Pride

Human blastocyst model by self-organization of naïve pluripotent stem cells

Project description:Human naïve pluripotent cells can differentiate to extraembryonic trophoblast and hypoblast cells. Here we report formation of human blastocyst models by self-organization solely of naïve pluripotent stem cells. The embryo models comprise the three founding lineages, epiblast, trophoblast and hypoblast, arranged to mimic the natural blastocyst. Single-cell RNA sequencing validated the identity of each cell type.

2021-05-05 | GSE171820 | GEO

Expression data from mouse embryonic stem cells across a time course of Erk stimulation

Project description:Fgf signaling via Erk activation has been associated with both neural induction and the generation of a primed state for the differentiation of embryonic stem cells (ESCs) to all somatic lineages. To dissect the role of Erk in both ESC self-renewal and lineage specification we explore the requirements for this pathway in various in vitro differentiation settings. A combination of pharmacological inhibition of Erk signaling and genetic loss of function experiments reveal a role for Erk signaling in suppressing endodermal differentiation, but not neural specification. Activation of Erk signaling in ESCs de-represses primitive endoderm (PrE) gene expression as a consequence of inhibiting the pluripotent/epiblast network. The early response to Erk activation correlates with functional PrE priming while sustained Erk activity results in PrE differentiation. Taken together, our results suggest that Erk signaling suppresses pluripotent gene expression to enable endodermal differentiation. We use microarray analysis to determine the transcription response to Erk1/2 in mouse embryonic stem cells across a 24 hour window of time Mouse ESCs carrying a tamoxifen inducible constitutively active c-Raf fusion protein were stimulated for 6 time points (30minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours) in the presence of 250nM PD173074. Uninduced (0h hours) and DMSO only treated cells served as controls.

2015-01-01 | E-GEOD-59755 | biostudies-arrayexpress

Expression data from mouse embryonic stem cells across a time course of Erk stimulation

2015-01-01 | GSE59755 | GEO