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Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential

ABSTRACT: Classical mouse embryology has established a paradigm of early development drivenby sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derivedfrom early epiblast have lost the potency to produce extraembryonic trophectoderm.We show in contrast that human naive epiblast cells readily make trophectoderm.Inhibition of ERK signalling, instrumental in naive stem cell propagation, unexpectedlypotentiates trophectoderm formation, an effect enhanced by Nodal inhibition.Transcriptome analyses authenticate conversion into trophectoderm with subsequentproduction of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Geneticperturbations indicate that NANOG suppresses and TFAP2C enables trophectoderminduction. Consistent with post-implantation progression, trophectoderm potential isextinguished in conventional human pluripotent stem cells, which instead makeamnion. Finally, human embryo epiblasts from late blastocysts efficiently generatetrophectoderm and differentiated trophoblast. Thus, pluripotent cells in the humanembryo retain extraembryonic lineage plasticity and regenerative potential untilimplantation. Harnessing this unanticipated regulative capacity may be beneficial forassisted reproduction technology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE166401 | GEO | 2021/02/09

REPOSITORIES: GEO

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Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential

Project description:Classical mouse embryology has established a paradigm of early development drivenby sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derivedfrom early epiblast have lost the potency to produce extraembryonic trophectoderm.We show in contrast that human naive epiblast cells readily make trophectoderm.Inhibition of ERK signalling, instrumental in naive stem cell propagation, unexpectedlypotentiates trophectoderm formation, an effect enhanced by Nodal inhibition.Transcriptome analyses authenticate conversion into trophectoderm with subsequentproduction of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Geneticperturbations indicate that NANOG suppresses and TFAP2C enables trophectoderminduction. Consistent with post-implantation progression, trophectoderm potential isextinguished in conventional human pluripotent stem cells, which instead makeamnion. Finally, human embryo epiblasts from late blastocysts efficiently generatetrophectoderm and differentiated trophoblast. Thus, pluripotent cells in the humanembryo retain extraembryonic lineage plasticity and regenerative potential untilimplantation. Harnessing this unanticipated regulative capacity may be beneficial forassisted reproduction technology.

2021-02-10 | GSE166422 | GEO

Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential II

Project description:Transcriptomic analysis confirms the trophoblast identity of the naïve pluripotent stem cell derived TSC cultures by comparing to the placenta derived TSC culture.

2021-02-20 | GSE167089 | GEO

RNA-seq of XTE cells and vesicles, XEN and XEN-like cells, and ES cells

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

Transcriptomics of trophoblast stem cells and extraembryonic endoderm stem cells

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

De novo formation of apical-basal polarity by Rap1 regulates epiblast patterning

Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.

2022-06-14 | PXD028315 | Pride

Chemical conversion of human conventional Pluripotent Stem Cells to Trophoblast Stem Cells following transient naive genes activation.

Project description:In human embryos, naive pluripotent cells of the inner cell mass (ICM) generate epiblast, primitive endoderm and trophectoderm (TE) lineage, whence trophoblast cells derive. In vitro, naive pluripotent stem cells (PSCs) retain this potential and efficiently generate trophoblast stem cells (TSCs), while conventional PSCs form TSCs at low efficiency. Transient histone deacetylase and MEK inhibitions with LIF stimulation is used to chemically reset conventional to naive PSCs. Here we report that chemical resetting induces expression of both naive and TSC markers and of placental imprinted genes. A modified chemical resetting protocol allows for the fast and efficient conversion of conventional PSCs into TSCs, entailing shutdown of pluripotency genes and full activation of the trophoblast master regulators, without induction of amnion markers. Chemical resetting generates a plastic intermediate state, characterised by co-expression of naive and TSC markers, after which cells steer towards one of the two fates in response to the signalling environment. The efficiency and rapidity of our system will be useful to study cell fate transitions, and to generate models of placental disorders.

2023-01-30 | GSE184562 | GEO

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]

2022-06-07 | GSE200960 | GEO

Human blastocyst model by self-organization of naïve pluripotent stem cells

Project description:Human naïve pluripotent cells can differentiate to extraembryonic trophoblast and hypoblast cells. Here we report formation of human blastocyst models by self-organization solely of naïve pluripotent stem cells. The embryo models comprise the three founding lineages, epiblast, trophoblast and hypoblast, arranged to mimic the natural blastocyst. Single-cell RNA sequencing validated the identity of each cell type.

2021-05-05 | GSE171820 | GEO

Capturing human trophoblast development with naive pluripotent stem cells in vitro [RNA-Seq]

Project description:Recent reports suggested human embryonic development is not always consistent with mouse. However, experimental approach to in vivo human embryos is extremely limited. Therefore, it is important to develop an appropriate in vitro cell culture system to analyse human pre-implantation development. In this report, we use human naive pluripotent stem cells (PSCs), which share features with pre-implantation epiblasts and show in vitro lineage specification of human trophoblast lineages. We successfully differentiated naive PSCs into trophectoderm, cytotrophoblast, syncytiotrophoblast, and extravillous trophoblast. Cytotrophoblasts could be cultured for long term as stem cells.

2021-04-07 | GSE144994 | GEO

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