Transcriptomics of trophoblast stem cells and extraembryonic endoderm stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE181334 | GEO | 2022/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:Embryonic (ES) and epiblast (EpiSC) stem cells are pluripotent but committed to an embryonic lineage fate. Conversely, trophoblast (TS) a nd extraembryonic endoderm (XEN) stem cells contribute predominantly to tissues of the placenta and yolk sac, respectively. Here we show that each of these four stem cell types is defined by a unique DNA methylation profile. Despite their distinct developmental origin, TS and XEN cells share key epigenomic hallmarks, chiefly characterized by robust DNA methylation of embryo-specific developmental regulators, as well as a subordinate role of 5-hydroxymethylation. We also observe a substantial methylation reinforcement of pre-existing epigenetic repressive marks that specifically occurs in extraembryonic stem cells compared to in vivo tissue, presumably due to continued high Dnmt3b expression levels. These differences establish a major epigenetic barrier between the embryonic and extraembryonic stem cell types. In addition, epigenetic lineage boundaries also separate the two extraembryonic stem cell types by mutual repression of key lineage-specific transcription factors. Thus, global DNA methylation patterns are a defining feature of each stem cell type that underpin lineage commitment and differentiative potency of early embryo-derived stem cells. Our detailed methylation profiles identify a cohort of developmentally regulated sequence elements, such as orphan CpG islands, that will be most valuable to uncover novel transcriptional regulators and pivotal M-^QM-^QgatekeeperM-^RM-^R genes in pluripotency and lineage differentiation.
2013-07-03 | E-MTAB-1754 | biostudies-arrayexpress
Project description:Bivalent histone domains have been proposed to contribute to pluripotency in embryonic stem cells, suggesting an epigenetic mechanism may regulate stem cell behavior in general. Here we compare histone modifications in two other stem cells derived from the blastocyst. We show that extraembryonic stem cells have little repressive lysine 27 trimethylation and few bivalent domains. Thus, bivalent domains are not a common mechanism for maintaining the undifferentiated state in blastocyst-derived stem cells and alternative mechanisms must mediate transcriptional repression in extraembryonic cells. We show that lysine 9 trimethylation, but not DNA methylation, is likely to fulfill this role. Intriguingly, although we do detect bivalent domains in pluripotent cells in the early mouse embryo, the epigenetic status of extraembryonic cells does not entirely reflect their in vitro stem cell counterparts. Therefore, differences in epigenetic regulation between lineage progenitors in vivo and in vitro may arise during selection for self-renewal in vitro. Expression profiles [GSM388878-GSM388881] of three different stem cells (R1 embryonic stem cells, trophoblast stem cells, extraembryonic endoderm stem cells) were generated for comparison to CHIP-seq data [GSM392044-GSM392055] of the same three stem cell lines to observe correlations with Histone 3 K4 and K27 trimethylation patterns. CHIP-seq details: R1 embryonic stem cells, trophoblast stem cells or extraembryonic endoderm stem cells were grown, lysed and chromatin purified. The chromatin was immunoprecipitated for either histone 3 K4 trimethylation or histone 3 K27 trimethylation and the immunoprecipitate was subjected to purification and high-throughput Illumina-based sequencing.
2010-05-16 | E-GEOD-15519 | biostudies-arrayexpress
Project description:Transcriptomics of trophoblast stem cells and extraembryonic endoderm stem cells
| PRJNA751593 | ENA
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
Project description:XEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm. The experiment was performed to gain insight into genes regulated by BMP and activin in XEN cells, and also to more precisely define the VE subtypes formed in culture. IM8A1 XEN cells were treated for 6 days with BMP2 (20 ng/ml, R&D Systems), activin A (30 ng/ml, Peprotech), both, or neither in GMEM + 10% fetal bovine serum.
2011-11-10 | E-GEOD-32199 | biostudies-arrayexpress
Project description:While the reprogramming factors OCT4, SOX2, KLF4, and MYC (OSKM) can reactivate the pluripotency network in terminally differentiated cells, they also regulate expression of non-pluripotency genes in other contexts, such as the mouse primitive endoderm. The primitive endoderm is an extraembryonic lineage established alongside the pluripotent epiblast in the blastocyst, and is the progenitor pool for extraembryonic endoderm stem (XEN) cells. Several studies have shown that endodermal genes are upregulated in fibroblasts undergoing reprogramming, although whether endodermal genes promote or inhibit acquisition of pluripotency is unclear. We show that, in fibroblasts undergoing conventional reprogramming, OSKM-induced expression of endodermal genes leads to formation of induced XEN (iXEN) cells, which possess key properties of blastocyst-derived XEN cells, including morphology, transcription profile, self-renewal, and multipotency. Our data show that iXEN cells arise in parallel to iPS cells, indicating that OSKM are sufficient to drive cells to two distinct fates during reprogramming. Sequence-based mRNA transcriptional profiling of three different cell lines (MEF, XEN, iXEN) with multiple biological replicates, under two different growth medium conditions (ESC medium, XEN medium) for XEN and iXEN cells.
2016-03-03 | E-GEOD-77550 | 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. 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:XEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm. The experiment was performed to gain insight into genes regulated by BMP and activin in XEN cells, and also to more precisely define the VE subtypes formed in culture.
2011-11-10 | GSE32199 | GEO
Project description:A blastocyst consists of three distinctive cell types: epiblast (EPI), trophoblast (TB), and primitive endoderm (PrE). Stem cell lines representing EPI and TB (embryonic stem (ES) cells and trophoblast stem (TS) cells) have been derived and they contribute to epiblast derivatives and trophoblast derivatives of stem cell-blastocyst chimeras, respectively. Although derived from PrE, extraembryonic endoderm (XEN) cells contribute to only a limited part of parietal endoderm (PE) but rarely to other PrE derivatives. Here we describe the establishment of primitive endoderm stem (PrES) cell lines in mice. PrES cells were derived and maintained in a serum-free media containing CHIR99021, FGF4, heparin, and PDGF-AA. RNA-seq analysis revealed that the transcriptome of PrES cells is globaly different from XEN cells: PrES cells express not only endoderm markers (Dab2, Gata4, Gata6, Sox17, etc.), but also pluripotent markers (Pou5f1, Cdh1, Nanog, Zfp42, etc.), and resembles in vivo founder PrE. PrES cells were rapidly and efficiently incorporated into PrE after blastocyst injection and efficiently contributed to all PrE derivatives, including PE, VE (visceral endoderm), and MZE (marginal zone endoderm) in chimeras. Importantly, PrES cells rescued embryonic lethality of PrE-depleted blastocysts by complementing all PrE derivatives. PrES cells thus not only contribute to understanding of the mechanisms of PrE specification but also provide a critical resource for artificial embryo reconstitution by stem cells alone.
2020-05-30 | GSE130957 | GEO
Project description:Extraembryonic trophoblast stem cells (TSC) can be converted to induced pluripotent stem cells (TSC-iPSCs) by overexpressing Oct4, Sox2, Klf4 and cMyc.
2011-02-01 | GSE25872 | GEO