Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential II
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE167089 | GEO | 2021/02/20
REPOSITORIES: GEO
Similar Datasets
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
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.
2021-02-09 | GSE166401 | GEO
Project description:Classic embryological experiments have established that the early mouse embryo develops via sequential lineage bifurcations. The first segregated lineage is the trophectoderm, essential for blastocyst formation. Mouse naive epiblast and derivative embryonic stem cells are restricted accordingly from producing trophectoderm. Here we show, in contrast, that human naive embryonic stem cells readily make blastocyst trophectoderm and descendant trophoblast cell types. Trophectoderm was induced rapidly and efficiently by inhibition of ERK/mitogen-activated protein kinase (MAPK) and Nodal signaling. Transcriptome comparison with the human embryo substantiated direct formation of trophectoderm with subsequent differentiation into syncytiotrophoblast, cytotrophoblast, and downstream trophoblast stem cells. During pluripotency progression lineage potential switches from trophectoderm to amnion. Live-cell tracking revealed that epiblast cells in the human blastocyst are also able to produce trophectoderm. Thus, the paradigm of developmental specification coupled to lineage restriction does not apply to humans. Instead, epiblast plasticity and the potential for blastocyst regeneration are retained until implantation.
| S-EPMC8189439 | biostudies-literature
Project description:Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential
| PRJNA700707 | ENA
Project description:Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential
| PRJNA700867 | ENA
Project description:Cells of the trophoblast lineage constitute the major part of placental tissues in higher mammals. Recent derivation of human trophoblast stem cells (TSC) from placental cytotrophoblasts (CT) and from blastocyst opens new opportunities for studying development and function of human placenta. Here we report that inhibition of TGF pathway leads to direct and robust conversion of primed human pluripotent stem cells into TSC. The resulting cell lines exhibit self-renewal, are able to differentiate into the main trophoblast lineages, and present RNA and epigenetic profiles that are indistinguishable from the TSC lines derived from placenta or blastocyst. Furthermore, activation of YAP pathway is necessary and sufficient for this conversion.
2022-09-21 | GSE213163 | GEO
Project description:Human Naïve Epiblast Cells Possess Unrestricted Lineage Potential II
| PRJNA702983 | ENA
Project description:Trophoblast stem cells (TSC) have recently been derived from human embryos, and early first trimester placenta; however, aside from ethical challenges, the unknown disease potential of these cells limits their scientific utility. We have previously established a BMP4-based two-step protocol for differentiation of primed human pluripotent stem cells (hPSC) into functional trophoblast; however, those trophoblast could not be maintained in a self-renewing TSC-like state. Here, we use the first step from this protocol, followed by a switch to a newly-developed TSC media, to derive bona-fide TSC. We show that these cells resemble placenta- and naïve hPSC-derived TSC, based on their transcriptome, as well as in vitro and in vivo differentiation potential. We conclude that primed hPSC can be used to generate functional TSC, through a simple protocol which can be applied to a widely-available set of existing hPSC, including induced pluripotent stem cells derived from patients with known birth outcomes.
2022-05-16 | GSE182790 | GEO
Project description:Trophoblast stem cells (TSC) have recently been derived from human embryos, and early first trimester placenta; however, aside from ethical challenges, the unknown disease potential of these cells limits their scientific utility. We have previously established a BMP4-based two-step protocol for differentiation of primed human pluripotent stem cells (hPSC) into functional trophoblast; however, those trophoblast could not be maintained in a self-renewing TSC-like state. Here, we use the first step from this protocol, followed by a switch to a newly-developed TSC media, to derive bona-fide TSC. We show that these cells resemble placenta- and naïve hPSC-derived TSC, based on their transcriptome, as well as in vitro and in vivo differentiation potential. We conclude that primed hPSC can be used to generate functional TSC, through a simple protocol which can be applied to a widely-available set of existing hPSC, including induced pluripotent stem cells derived from patients with known birth outcomes.
2022-05-16 | GSE182789 | GEO
Project description:Cells of the trophoblast lineage constitute the major part of placental tissues in higher mammals. Recent derivation of human trophoblast stem cells (TSC) from placental cytotrophoblasts (CT) and from blastocyst opens new opportunities for studying development and function of human placenta. Here we report that inhibition of TGF pathway leads to direct and robust conversion of primed human pluripotent stem cells into TSC. The resulting cell lines exhibit self-renewal, are able to differentiate into the main trophoblast lineages, and present RNA and epigenetic profiles that are indistinguishable from the TSC lines derived from placenta or blastocyst. Furthermore, activation of YAP pathway is necessary and sufficient for this conversion.
2022-09-21 | GSE192917 | GEO