Hypoblast from human pluripotent stem cells regulates epiblast development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA544653 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24763900_1.fastq.gz | Fastqsanger.gz | |||
| SRR24763900_2.fastq.gz | Fastqsanger.gz | |||
| SRR24764000_1.fastq.gz | Fastqsanger.gz | |||
| SRR24764000_2.fastq.gz | Fastqsanger.gz | |||
| SRR24763901_1.fastq.gz | Fastqsanger.gz |
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Project description:Hypoblast from human pluripotent stem cells regulates epiblast development [RNA-seq]
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Project description:Hypoblast from human pluripotent stem cells regulates epiblast development [scRNA-seq]
| PRJNA977648 | ENA
Project description:Recently, several studies using cultures of human embryos together with single-cell RNA-seq (scRNA-seq) analyses have revealed differences between humans and mice, necessitating the study of human embryos. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation stage studies. Thus, recent efforts have focused on developing in vitro self-organising models using human stem cells. Here, we established a genetic approach to generate authentic hypoblast cells (nHyC) - known to give rise to one of the two extraembryonic tissues essential for embryonic development - from naïve human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with naïve hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naïve hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to grow due to IL6 secreted by the trophectoderm. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pre-gastrula stage, whose emergence can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We therefore model and reveal mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.
2023-10-17 | GSE233715 | GEO
Project description:Recently, several studies using cultures of human embryos together with single-cell RNA-seq (scRNA-seq) analyses have revealed differences between humans and mice, necessitating the study of human embryos 1-8. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation stage studies. Thus, recent efforts have focused on developing in vitro self-organising models using human stem cells 9-18. Here, we established a genetic approach to generate authentic hypoblast cells (nHyC) - known to give rise to one of the two extraembryonic tissues essential for embryonic development - from naïve human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with naïve hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naïve hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to grow due to IL6 secreted by the trophectoderm. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pre-gastrula stage, whose emergence can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We therefore model and reveal mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.
2023-10-17 | GSE233959 | GEO
Project description:Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human embryos1-8. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation-stage studies. Thus, recent efforts have focused on developing in vitro self-organizing models using human stem cells9-17. Here, we report genetic and non-genetic approaches to generate authentic hypoblast cells (naive hPSC-derived hypoblast-like cells (nHyCs))-known to give rise to one of the two extraembryonic tissues essential for embryonic development-from naive human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with naive hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional naive hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to develop in response to trophectoderm-secreted IL-6. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pregastrula stage, the emergence of which can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We have therefore successfully modelled and identified the mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.
| S-EPMC10849967 | biostudies-literature
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
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 | GSE297478 | GEO
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
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-17 | GSE131747 | GEO