Epigenetic landscape of expanded potential stem cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Mus musculus
SUBMITTER:
PROVIDER: E-ERAD-426 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Despite intensive efforts, establishing porcine embryonic stem cells have been challenging. We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the activity of critical molecular pathways that predisposes lineage differentiation in the mouse preimplantation embryo. EPSCs had enriched molecular signatures of blastomeres and possessed the developmental potency to all embryonic and extraembryonic cell lineages. In this study, we report the derivation of porcine EPSC (pEPSC) lines either directly from preimplantation embryos or by reprogramming fetal fibroblasts. Under similar culture conditions, human ESCs and iPSCs can be converted, or somatic cells are directly reprogrammed, to EPSCs (hEPSCs) that display the molecular and functional attributes reminiscent of pEPSCs. Here, we performed ChIP-seq experiments of H3K4me3 and H3K27me3 to characterise the epigenetic signatures of the EPSCs.
2019-04-01 | E-MTAB-7252 | biostudies-arrayexpress
Project description:The zygote and blastomeres of a cleavage stage mouse embryo have the capacity to differentiate to all lineages in the embryo proper and extraembryonic tissues and are considered totipotent. Mouse ESCs can differentiate to embryonic lineages but have restricted potential to trophoblasts. We report here that cultures of a new type of stem cells with expanded potential (EPSCs) can be established from in vitro cultured mouse preimplantation embryos and individual blastomeres, from directly converting mouse ESCs, or from genetically reprogramming somatic cells. EPSCs differentiate to trophoblasts in vitro, and a single EPSC contributes in chimeras to both extraembryonic lineages including the placenta trophoblasts and the embryo proper. Molecular analyses reveal that EPSCs express core pluripotency factors similar to ESCs, but have enriched signature of preimplantation blastomeres. The data described here suggest that similar cell lines from other mammalian species might also be established in culture and stably maintained.
2014-08-27 | E-ERAD-285 | biostudies-arrayexpress
Project description:Despite intensive efforts, establishing porcine embryonic stem cells have been challenging. We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the activity of critical molecular pathways that predisposes lineage differentiation in the mouse preimplantation embryo. EPSCs had enriched molecular signatures of blastomeres and possessed the developmental potency to all embryonic and extraembryonic cell lineages. In this study, we report the derivation of porcine EPSC (pEPSC) lines either directly from preimplantation embryos or by reprogramming fetal fibroblasts. Under similar culture conditions, human ESCs and iPSCs can be converted, or somatic cells are directly reprogrammed, to EPSCs (hEPSCs) that display the molecular and functional attributes reminiscent of pEPSCs. Here, we performed RNA-seq experiments to characterise the transcriptional signatures of the EPSCs.
2019-04-01 | E-MTAB-7253 | biostudies-arrayexpress
Project description:Despite intensive efforts, establishing porcine embryonic stem cells have been challenging. We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the activity of critical molecular pathways that predisposes lineage differentiation in the mouse preimplantation embryo. EPSCs had enriched molecular signatures of blastomeres and possessed the developmental potency to all embryonic and extraembryonic cell lineages. In this study, we report the derivation of porcine EPSC (pEPSC) lines either directly from preimplantation embryos or by reprogramming fetal fibroblasts. Under similar culture conditions, human ESCs and iPSCs can be converted, or somatic cells are directly reprogrammed, to EPSCs (hEPSCs) that display the molecular and functional attributes reminiscent of pEPSCs. Here, we performed Single-Cell RNA-seq experiments to characterise the transcriptional heterogeneity of the EPSCs.
2019-04-01 | E-MTAB-7254 | biostudies-arrayexpress
Project description:Embryonic stem cells (ESCs) and induced pluripotent stem cells have the potential to differentiate to all cell types of an adult individual and are useful for studying development and for translational research. However, extrapolation of mouse and human ESC knowledge to deriving stable ESC lines of domestic ungulates and large livestock species has been challenging. In contrast to ESCs that are usually established from the blastocyst, mouse expanded potential stem cells (EPSCs) are derived from four-cell and eightcell embryos. We have recently used the EPSC approach and established stem cells from porcine and human preimplantation embryos. EPSCs are molecularly similar across species and have broader developmental potential to generate embryonic and extraembryonic cell lineages. We further explore the EPSC technology for mammalian species refractory to the standard ESC approaches and report here the successful establishment of bovine EPSCs (bEPSCs) from preimplantation embryos of both wild-type and somatic cell nuclear transfer. bEPSCs express high levels of pluripotency genes, propagate robustly in feeder-free culture, and are genetically stable in long-term culture. bEPSCs have enriched transcriptomic features of early preimplantation embryos and differentiate in vitro to cells of the three somatic germ layers and, in chimeras, contribute to both the embryonic (fetal) and extraembryonic cell lineages. Importantly, precise gene editing is efficiently achieved in bEPSCs, and genetically modified bEPSCs can be used as donors in somatic cell nuclear transfer. bEPSCs therefore hold the potential to substantially advance biotechnology and agriculture.
2021-04-12 | GSE129760 | GEO
Project description:Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.
2022-04-18 | GSE157720 | GEO
Project description:Naïve pluripotent and expanded potential stem cells (EPSCs) represent the pre-implantation epiblast which are molecularly, epigenetically and developmentally distinct from conventional primed pluripotent stem cells representing the epiblast of post-implantation embryo. These stem cell types offer expanded developmental potential towards extraembryonic tissues, clonality at the single cell level, high homogeneity and are more amenable for genome engineering. Here we use a polycistronic cassette to directly reprogram fibroblasts into induced EPSCs without a detour to primed pluripotency. When we replace SOX2 with engineered SOX17 factor (eSOX17), we obtain 7 to 10 -fold more iEPSC colonies within shorter time periods. We next tested our reprogramming regimen in four media supporting naïve pluripotency reprogramming and could reproducibly obtain large numbers of clonally expandable colonies with eSOX17 whilst SOX2 occasionally fails. The resultant naïve pluripotent and expanded potential stem cells molecularly and functionally resemble their counterparts derived from embryonic stem cells. In sum, the use of engineered SOX17 factor enables a direct, fast, efficient and reproducible reprogramming of somatic cells into cells representative of the pre-implantation epiblast from somatic cells.
2024-03-01 | GSE225298 | GEO
Project description:Extended pluripotent stem cells (EPSCs) are a novel cell type derived from 8-cell stage embryo or conversion of pluripotent stem cells using a chemical cocktail that blocks the cell fate decision. Previous studies have defined various aspects of EPSCs including dual differentiational potency to both extraembryonic and embryonic lineages, their ability to directly transfer extended pluripotency to differentiated somatic cells by cell fusion remains unelucidated. Here, we sought to determine whether somatic cells could be reprogrammed and obtain extended pluripotency. In this study, newly derived EPSCs are fused with neural stem cells, which is somatic stem cells, by polyethylene glycol (PEG)-mediated method. The resulting hybrid cells exhibited pluripotential properties with upregulated EPSC-specific genes. Also, hybrid cells contributed to the embryonic and extraembryonic lineages in vivo and in vitro. RNA-sequencing analysis confirmed that the global gene expression pattern of hybrid cells are similar to EPSC while there is no expression of NSC markers, indicating complete erasure of somatic memory after fusion reprogramming. Lastly, EPSCs and hybrids exhibited a bivalent energy metabolism phenotype or more active oxidative phosphorylation (OXPHOS) and glycolysis than NSCs. In conclusion, the extended pluripotency of EPSCs could be transferred to somatic cells through fusion-induced reprogramming.
2022-08-07 | GSE210520 | GEO
Project description:Extended pluripotent or expanded potential stem cells (EPSCs) possess the superior developmental potential to embryonic stem cells (ESCs). However, the molecular underpinning of their in vitro maintenance is not well defined. We comparatively studied transcriptome, chromatin accessibility, active histone modification chromatin marks and relative proteomes of ESCs and the two well-established EPSCs to probe the molecular foundation of their unique developmental potential. We found a great overlap in the transcriptomic and chromatin accessibility profiles and reliance on pluripotency factors Oct4, Sox2, and Nanog for self-renewal between ESCs and EPSCs. Importantly, we identified a subset of genomic, transcriptomic, and proteomic signatures that distinguish EPSCs from ESCs in transcriptional and translational regulation as well as epigenetic and metabolic control. We also identified molecular differences between the two well-established EPSCs. Our study provides a rich resource for dissecting the regulatory network underlying the developmental potency of EPSCs and exploring alternative states of totipotency.
2022-07-19 | GSE201303 | GEO
Project description:Extended pluripotent or expanded potential stem cells (EPSCs) possess the superior developmental potential to embryonic stem cells (ESCs). However, the molecular underpinning of their in vitro maintenance is not well defined. We comparatively studied transcriptome, chromatin accessibility, active histone modification chromatin marks and relative proteomes of ESCs and the two well-established EPSCs to probe the molecular foundation of their unique developmental potential. We found a great overlap in the transcriptomic and chromatin accessibility profiles and reliance on pluripotency factors Oct4, Sox2, and Nanog for self-renewal between ESCs and EPSCs. Importantly, we identified a subset of genomic, transcriptomic, and proteomic signatures that distinguish EPSCs from ESCs in transcriptional and translational regulation as well as epigenetic and metabolic control. We also identified molecular differences between the two well-established EPSCs. Our study provides a rich resource for dissecting the regulatory network underlying the developmental potency of EPSCs and exploring alternative states of totipotency.
2022-07-19 | GSE201301 | GEO