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Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero.

ABSTRACT: Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero.

PROVIDER: PRJNA827763 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18790504.fastq.gz	Fastqsanger.gz
	SRR18790505.fastq.gz	Fastqsanger.gz
	SRR18790506.fastq.gz	Fastqsanger.gz
	SRR18790507.fastq.gz	Fastqsanger.gz
	SRR18790508.fastq.gz	Fastqsanger.gz

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Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [scRNAseq]

Project description:The embryo instructs the allocation of cell states to spatially regulate growth and functions. In the blastocyst, the formation and divergence of the trophoblast lineage ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the inner epiblast cells (inducers) that captures stable, highly self-renewing, pre-implantation-like mouse trophectoderm stem cells (TESCs). When exposed to suboptimal inducers, these stem cells form interconvertible subpopulations with reduced self-renewal, known as trophoblast stem cells (TSCs), and resembling peri-implantation progenitors. TECSs have an enhanced capacity to form blastoids that implant more efficiently in utero. We find that this enhanced capacity is due to epiblast inducers not only controlling trophoblast growth but also trophoblast secretion of WNT6/7B that stimulates uterine decidualization. Thus, the embryo leverages epiblast inductions to drive both the growth and decidualization potential of trophoblasts required for implantation and development.

2022-06-07 | GSE200958 | GEO

Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [bulk RNA-Seq]

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Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [scRNAseq]

Project description:Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [scRNAseq]

| PRJNA827775 | ENA

Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [bulk RNA-Seq]

Project description:Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [bulk RNA-Seq]

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Human blastoids model blastocyst development and implantation

Project description:About one week after fertilization, human embryos implant into the uterus. This necessitates the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (PXGL hPSCs) efficiently (>70%) form blastoids generating blastocyst-stage analogs of the 3 founding lineages (>97% trophectoderm, epiblast, and primitive endoderm) according to the sequence and to the pace of blastocyst development. Blastoids form the first axis and we observe that the epiblast induces the maturation of the polar trophectoderm that consequently acquires the specific and transient potential to attach to hormonally-stimulated endometrial cells. Such human blastoids are faithful, scalable, versatile, and ethical models to explore human implantation and development.

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Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-07 | GSE200961 | GEO

The chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids.

Project description:The early mammalian conceptus (blastocyst) contains two supporting extraembryonic tissues - the trophectoderm and the primitive endoderm (PrE) - that encase and guide the epiblast (Epi) to eventually form the all body. Modifications of the conceptus exposed key genes regulating these tissues co-development. However, the combination of signalling pathways at play remains elusive. Stem cell-based models including embryoid bodies and blastoids can be generated in large numbers and subjected to high-content screens. Here, we use combinatorial screens of proteins, GPCR ligands and small molecules to rapidly (<96 hours) and efficiently (80%) guide embryoid bodies to form a three dimensional PrE-/Epiblast-like niche in chemically-defined conditions (gel-free, serum-free). This bipotent niche spontaneously progresses, without growth factors, to form a pro-amniotic cavity surrounded by a polarized Epi covered by parietal and visceral endoderm-like cells. In blastoids, these molecules enhance the ratio and number of Gata6+/Nanog+ cells and promote the survival, expansion and morphogenesis of a post-implantation-like Epi in vitro. Altogether, modelling early development in chemically-defined conditions delineates the pathways sufficient to form a functional PrE/Epiblast niche that fuels post-implantation development.

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Project description:Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form blastocyst models, which we termed blastoid. Here we show that naïve human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGFb, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation (>95%) analogs of the three founding lineages (trophoblast, epiblast, hypoblast), and in the sequential and timely manner of blastocysts. Blastoids spontaneously form an axis marked by maturation of the polar region, which acquires the potential to specifically attach to hormonally-stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development.

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Project description:Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Appropriate stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGF-β, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation analogs of the three founding lineages (trophoblast, epiblast, primitive endoderm; >97%) according to the sequence and pace of blastocyst development. Blastoids spontaneously form an axis marked by the maturation of the polar region, which acquires the potential to specifically attach to hormonally stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development.

2021-09-15 | GSE179040 | GEO

Single-cell RNA-seq for mouse NrESC-blastoids

Project description:Embryonic stem cells upon extrinsic induction could self-assemble into blastocyst-like structures. However, the intrinsic regulation of such blastoid forming potential remain to be addressed. We discover that the activity of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) in expanded potential stem cell (EPSC) positively correlates with blastoid efficiency and quality. In addition, Nr1h2 agonist, T0901317, improves natural blastocyst development. Surprisingly, Nr1h2-activated ESC (NrESC) is rewired towards a distinct pluripotency state that is capable of self-organizing into blastoids and contribute to embryonic and extraembryonic lineage. We aim at characterizing the NrESC-derived blastoids by single-cell RNA-seq and show that blastoid comprise of epiblast-like, trophectoderm-like and primitive endoderm-like populations, which is the same as blastocyst composition and shows respective gene marker expression for each cluster. Thus, NrESC has attained a unique expanded pluripotency state driven by Nr1h2 activation.

2024-10-23 | GSE217826 | GEO

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