Establishment of bovine extraembryonic endoderm stem cells enables efficient blastoid formation
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ABSTRACT:
PROVIDER: PRJNA1191491 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31538504_1.fastq.gz | Fastqsanger.gz | |||
| SRR31538504_2.fastq.gz | Fastqsanger.gz | |||
| SRR31538505_1.fastq.gz | Fastqsanger.gz | |||
| SRR31538505_2.fastq.gz | Fastqsanger.gz | |||
| SRR31538506_1.fastq.gz | Fastqsanger.gz |
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Project description:Extraembryonic endoderm stem (XEN) cells resemble the primitive endoderm of blastocyst and provide valuable alternatives for understanding hypoblast development and building stem cell-based embryo models. Here we report that a chemical cocktail (FGF4, BMP4, IL-6, XAV939, and A83-01) enables the de novo derivation and long-term culture of bovine XENs (bXENs) from blastocysts. Transcriptomic and epigenomic analyses confirm the identity of bXENs and reveal that bXENs resemble the hypoblast lineages of early bovine peri-implantation embryos. Furthermore, we show that bXENs maintain the stemness of expanded embryonic stem cells (EPSCs) and prevent them from differentiation. The chemical cocktail sustaining bXENs also facilitates the growth of epiblasts in developing pre-implantation embryos. Finally, 3D assembly of bXENs with bovine EPSCs and trophoblast stem cells (TSCs) enables efficient generation of blastoids that resemble blastocysts. Bovine XENs and blastoids established here represent accessible in vitro models for understanding embryogenesis and improving reproductive efficiency in domestic livestock.
2025-02-12 | GSE283042 | GEO
Project description:The visceral endoderm (VE) is an epithelial tissue in the early postimplantation mouse embryo that encapsulates the pluripotent epiblast distally and the extraembryonic ectoderm proximally. In addition to facilitating nutrient exchange before the establishment of a circulation, the VE is critical for patterning the epiblast. Since VE is derived from the primitive endoderm (PrE) of the blastocyst, and PrE-derived eXtraembryonic ENdoderm (XEN) cells can be propagated in vitro, XEN cells should provide an important tool for identifying factors that direct VE differentiation. In this study, we demonstrated that BMP4 signalling induces the formation of a polarized epithelium in XEN cells. This morphological transition was reversible, and was associated with the acquisition of a molecular signature comparable to extraembryonic (ex) VE. Resembling exVE which will form the endoderm of the visceral yolk sac, BMP4-treated XEN cells regulated hematopoiesis by stimulating the expansion of primitive erythroid progenitors. We also observed that LIF exerted an antagonistic effect on BMP4-induced XEN cell differentiation, thereby impacting the extrinsic conditions used for the isolation and maintenance of XEN cells in an undifferentiated state. Taken together, our data suggest that XEN cells can be differentiated towards an exVE identity upon BMP4 stimulation, and therefore represent a valuable tool for investigating PrE lineage differentiation. Total RNA isolated in triplicate from XEN stem cell cultures that were untreated (samples 1-3) or treated with BMP4 growth factor (samples 4-6). Total RNA isolated in triplicate from XEN stem cells that were treated with BMP4 and were flow sorted as Afp::GFP-positive (samples 7-9) or Afp::GFP-negative (samples 10-12).
2011-09-13 | E-GEOD-32094 | biostudies-arrayexpress
Project description:The visceral endoderm (VE) is an epithelial tissue in the early postimplantation mouse embryo that encapsulates the pluripotent epiblast distally and the extraembryonic ectoderm proximally. In addition to facilitating nutrient exchange before the establishment of a circulation, the VE is critical for patterning the epiblast. Since VE is derived from the primitive endoderm (PrE) of the blastocyst, and PrE-derived eXtraembryonic ENdoderm (XEN) cells can be propagated in vitro, XEN cells should provide an important tool for identifying factors that direct VE differentiation. In this study, we demonstrated that BMP4 signalling induces the formation of a polarized epithelium in XEN cells. This morphological transition was reversible, and was associated with the acquisition of a molecular signature comparable to extraembryonic (ex) VE. Resembling exVE which will form the endoderm of the visceral yolk sac, BMP4-treated XEN cells regulated hematopoiesis by stimulating the expansion of primitive erythroid progenitors. We also observed that LIF exerted an antagonistic effect on BMP4-induced XEN cell differentiation, thereby impacting the extrinsic conditions used for the isolation and maintenance of XEN cells in an undifferentiated state. Taken together, our data suggest that XEN cells can be differentiated towards an exVE identity upon BMP4 stimulation, and therefore represent a valuable tool for investigating PrE lineage differentiation.
2011-09-14 | GSE32094 | GEO
Project description:Extraembryonic mesoderm (ExM) is one of the first cell types that emerges during embryogenesis and constitutes essential supportive tissues for the pregnancy. Primate ExM is known to form prior to gastrulation, unlike its murine counterpart which is derived from the primitive streak. Based on the embryonic morphology and the proximity of ExM to the extraembryonic endoderm (hypoblast), we hypothesised that ExM can be derived in vitro from the naïve extraembryonic endoderm (nEnd) cell line. We applied a mesoderm differentiation protocol, which has been reported to induce ExM from mouse epiblast stem cells, on human nEnd and analysed the transcriptome on day 0, 1, 2, 8 and 15.
2023-06-29 | E-MTAB-12517 | biostudies-arrayexpress
Project description:Understanding the mechanisms of hypoblast development and its role in the implantation is critical for improving farm animal reproduction, but it is hampered by the lack of research models. Here we report that a chemical cocktail (FGF4, BMP4, IL-6, XAV939, and A83-01) enables de novo derivation and long-term culture of bovine extraembryonic endoderm cells (bXENs). Transcriptomic and epigenomic analyses confirmed the identity of bXENs and revealed that they are resemble hypoblast lineages of early bovine peri-implantation embryos. We showed that bXENs help maintain the stemness of bovine ESCs and prevent them from differentiation. In the presence of a signaling cocktail sustaining bXENs, the growth and progression of epiblasts are also facilitated in the developing pre-implantation embryo. Furthermore, through 3D assembly of bXENs with bovine ESCs and TSCs, we developed an improved bovine blastocyst like structure (bovine blastoid) that resembles blastocyst. The bovine XENs and blastoids established in this study represent accessible in vitro models for understanding hypoblast development and improving reproductive efficiency in livestock species.
| S-EPMC11702706 | biostudies-literature
Project description:To identify splicing regulators with unique regulation in placenta and the trophectoderm lineage, we sequenced trophoblast stem (TS) and Extraembryonic endoderm stem (XEN) cells.
2022-07-01 | GSE181334 | GEO
Project description:The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast (TB), and primitive endoderm (PrE). Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the functional properties of Epi and TB, the currently available extraembryonic endoderm cells (XENC) do not fully recapitulate the developmental potential of PrE. Here we report derivation of primitive endoderm stem cells (PrESCs) in mice. PrESCs express both PrE and pluripotency marker genes like founder PrE. These cells are efficiently incorporated into PrE upon blastocyst injection, generate functionally competent PrE-derived tissues, and support fetal development of PrE-depleted blastocysts in chimeras. Establishment of PrESCs therefore represents a significant step-forward in elucidating the mechanisms for PrE specification and subsequent pre- and post-implantation development.
2021-12-31 | GSE185461 | GEO
Project description:Induction of the Arf tumor suppressor in response to hyperproliferative stress following oncogene activation activates a p53-dependent transcriptional program that limits the expansion of incipient cancer cells. Although Arf is not expressed in most tissues of fetal or young adult mice, it is physiologically expressed in the fetal yolk sac, a tissue derived from the extraembryonic endoderm. We demonstrate that expression of the mouse p19Arf protein marks late stages of extraembryonic endoderm differentiation in cultured embryoid bodies derived from either embryonic stem cells or induced pluripotent stem cells, and that Arf inactivation specifically delays the differentiation of the extraembryonic endoderm lineage, but not the formation of other germ cell lineages from pluripotent progenitors. Arf is required for the timely induction of extraembryonic endodermal cells in response to Ras/Erk signaling and, in turn, acts through p53 to ensure extraembryonic endoderm lineage development, but not maintenance. Remarkably, a significant temporal delay in extraembryonic endoderm differentiation detected during the maturation of Arf-null embryoid bodies is rescued by enforced expression of miR-205, a micro-RNA up-regulated by p19Arf and p53. Introduction of miR-205 into Arf-null embryonic stem cells rescues defective ExEn formation and elicits a program of gene expression that controls the migration and adhesion of embryonic endodermal cells. This occurs, at least in part, through atypical regulation of genes that control the epithelial-to-mesenchymal transition in cancer cells. Our findings suggest that noncanonical and canonical roles of Arf in extraembryonic endoderm development and tumor suppression, respectively, may be conceptually linked through mechanisms that govern cell-to-cell attachment and migration. 4 samples total two each at two time points in ESC development At each time point one sample was treted with miR-205 and the other with a GFP control vector
2013-04-01 | E-GEOD-42210 | biostudies-arrayexpress
Project description:Transcription factor-mediated reprogramming is a powerful method to study cell fate changes. In this work, we demonstrate that the transcription factor Gata6 can initiate reprograming of multiple cell types to induced extraembryonic endoderm (iXEN) cells. Intriguingly, Gata6 is sufficient to drive iXEN cells from mouse pluripotent cells and differentiated neural cells. Furthermore, GATA6 induction in human ES (hES) cells also downregulates pluripotency gene expression and upregulates extraembryonic endoderm genes, revealing a conserved function in mediating this cell fate switch. Profiling transcriptional changes following Gata6 induction in mES cells reveals step-wise pluripotency factor disengagement, with initial repression of Nanog and Esrrb, then Sox2 and finally Oct4, alongside step-wise activation of extraembryonic endoderm genes. Chromatin immunoprecipitation and subsequent high-throughput sequencing analysis shows Gata6 enrichment near both pluripotency and endoderm genes, suggesting that Gata6 functions as both a direct repressor and activator. Together this demonstrates that Gata6 is a versatile and potent reprogramming factor that can act alone to drive a cell fate switch from diverse cell types. Time-course microarray analysis of Gata6-mediated reprogramming from 12 to 144 hours of doxycycline treatment in mouse embryonic stem (mES) cells compared to uninduced mES cells, embryo-derived extraembryonic endoderm (XEN) cells and Sox7 overexpressing mES cells after 144 hours of doxycycline treatment.
2015-06-30 | E-GEOD-69321 | biostudies-arrayexpress
Project description:Extraembryonic endoderm stem (XEN) cells are isolated from PrE (primitive endoderm) of blastocysts. We directly obtained cell lines with XEN characteristics from porcine embryos for the first time. the RNA-seq data indicated highly reproducible gene expression patterns among piPSCs or pXEN-like cell.the gene expression patterns of pXEN-like cells were significantly different from those of piPSCs
2019-11-15 | GSE140414 | GEO