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Comparative functional genomics identifies unique molecular features of EPSCs [ATAC-seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE201301 | GEO | 2022/07/19

REPOSITORIES: GEO

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Comparative functional genomics identifies unique molecular features of EPSCs

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. This SuperSeries is composed of the SubSeries listed below.

2022-07-19 | GSE201305 | GEO

Comparative functional genomics identifies unique molecular features of EPSCs [RNA-seq]

2022-07-19 | GSE201303 | GEO

Comparative functional genomics identifies unique molecular features of EPSCs [ChIP-seq]

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Establishment in Culture of Mouse Expanded Potential Stem Cells

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

Establishment of Porcine and Human Expanded Potential Stem Cells (Single-Cell RNA-seq)

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

Establishment of Porcine and Human Expanded Potential Stem Cells (bulk RNA-seq)

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

Establishment of Porcine and Human Expanded Potential Stem Cells (ChIP-seq)

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

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Project description:Extended pluripotent stem cells (EPSCs) derived from mice and humans showed an enhanced potential for chimeric formation. By exploiting transcriptomic techniques, we assessed the differences in gene expression profile between extended EPSCs derived from mice and humans, and those newly derived from the common marmoset (marmoset; Callithrix jacchus). Although the marmoset EPSC-like cells displayed a unique colony morphology distinct from murine and human EPSCs, they displayed a pluripotent state akin to embryonic stem cells (ESCs), as confirmed by gene expression and immunocytochemical analyses of pluripotency markers and three-germ-layer differentiation assay. Importantly, the marmoset EPSC-like cells showed interspecies chimeric contribution to mouse embryos, such as E6.5 blastocysts in vitro and E8.5 epiblasts in vivo in mouse development. Also, we discovered that the perturbation of gene expression of the marmoset EPSC-like cells from the original ESCs resembled that of human EPSCs. Thus, we established the efficacy of the method for the derivation of marmoset EPSCs

2022-01-01 | GSE189633 | GEO

Gene expression profiles among hiPSCs, hiPSC-EpSCs and hEpSCs

Project description:Phenotypically comparing the hiPSC-EpSCs with hiPSCs and hEpSCs.

2014-02-11 | GSE51028 | GEO

Establishment of bovine expanded potential stem cells

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

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