Human blastocyst model by self-organization of naïve pluripotent stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171820 | GEO | 2021/05/05
REPOSITORIES: GEO
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Project description:Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form blastocyst models, which we termed blastoid. Here we show that naïve human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGFb, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation (>95%) analogs of the three founding lineages (trophoblast, epiblast, hypoblast), and in the sequential and timely manner of blastocysts. Blastoids spontaneously form an axis marked by maturation of the polar region, which acquires the potential to specifically attach to hormonally-stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development.
2021-09-15 | GSE177616 | GEO
Project description:Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Appropriate stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGF-β, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation analogs of the three founding lineages (trophoblast, epiblast, primitive endoderm; >97%) according to the sequence and pace of blastocyst development. Blastoids spontaneously form an axis marked by the maturation of the polar region, which acquires the potential to specifically attach to hormonally stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development.
2021-09-15 | GSE179040 | GEO
Project description:About one week after fertilization, human embryos implant into the uterus. This necessitates the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (PXGL hPSCs) efficiently (>70%) form blastoids generating blastocyst-stage analogs of the 3 founding lineages (>97% trophectoderm, epiblast, and primitive endoderm) according to the sequence and to the pace of blastocyst development. Blastoids form the first axis and we observe that the epiblast induces the maturation of the polar trophectoderm that consequently acquires the specific and transient potential to attach to hormonally-stimulated endometrial cells. Such human blastoids are faithful, scalable, versatile, and ethical models to explore human implantation and development.
2021-09-15 | GSE177689 | GEO
Project description:Rat Extraembryonic Endoderm Precursor (XEN-P) cells resemble the nascent hypoblast of the blastocyst. Here we show that rat Multipotent Adult Progenitor Cell (rMAPC) lines derived from bone marrow (BM) exhibit salient nascent hypoblast characteristics. We could not identify cells with hypoblast features in rat BM, but they appeared after prolonged in vitro culture under rMAPC conditions. However, rMAPC culture conditions supported the very rapid isolation of new lines with nascent hypoblast features from rat blastocysts that were more homogenous than XEN-P cells isolated on feeders. The gene expression profile, growth factor requirement, Oct4 promoter methylation, and in vitro/vivo differentiation potential of cells isolated using rMAPC culture conditions from BM or blastocysts or XEN-P cells were highly similar. We conclude that the three cell populations have characteristics of hypoblast stem cells (HypoSC) and that rMAPC culture conditions support the isolation of XEN-P/HypoSC from the blastocyst and induction of HypoSC from BM. Comparison between bone marrow and blastocyst-derived Hypoblast Stem Cells (hypoSC) Three cell lines derived from bone marrow, three cell lines derived from blastocyst and one mesenchymal used, as control (for all of them 2 replicates)
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Project description:The human embryo undergoes morphogenetic transformations following implantation into the uterus and yet our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Here, we establish a stem cell-derived human post-implantation embryo model comprised of embryonic and extraembryonic tissues. Overexpression of the transcription factors GATA6 and SOX17 or GATA3 and AP2g in hESCs allowed us to generate hypoblast-like and trophoblast-like cells, respectively. We established conditions to combine these extraembryonic-like cells with wildtype embryonic stem cells and promote their self-organization into structures that mimic aspects of the post-implantation human embryo. These aggregates contain an inner pluripotent epiblast-like domain surrounded by both hypoblast- and trophoblast-like tissues. We show that this human embryo stem cell model robustly generates several cell types, including amnion-, extraembryonic mesenchyme- and primordial germ cell-like cells. Using perturbation experiments, we demonstrated that these populations arise in response to BMP signaling. This model also allowed us to identify an inhibitory role for SOX17 in the specification of anterior hypoblast-like cells. Modulation of the subpopulations in the hypoblast-like compartment demonstrated that these extraembryonic-like cells impact epiblast-like domain differentiation, highlighting functional tissue-tissue crosstalk. In conclusion, this modular, tractable model of the human embryo that includes both embryonic- and extraembryonic-like cells has the potential to probe key questions of human post-implantation development.
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Project description:Our ability to study early human post-implantation development remains highly limited due to the ethical and technical challenges associated with intrauterine development of the human embryo after implantation. Despite the great progress made on human blastoids or gastruloids, such elegant models do not constitute an integrated synthetic stem cell-derived embryoid models (SEMs) that includes all the key extra-embryonic tissues of the early pre-gastrulating implanted human conceptus (e.g. hypoblast, yolk-sac, trophoblasts, amnion and extraembryonic mesoderm), and thus, do not recapitulate post-implantation epiblast development within the context of these extra-embryonic compartments. Mouse naïve pluripotent stem cells (PSCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse SEMs, while bypassing the blastocyst-like stage, and eventually initiating organogenesis ex utero. Here, we implement critical adaptations to extend these finding in humans, using only genetically unmodified human naïve PSCs, circumventing the need for ectopic expression of lineage promoting transgenes. Such integrated human SEMs recapitulate all known compartments of early post-implantation stage human embryos, including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity and a connective stalk. This new platform constitutes a tractable stem cell-based model for experimentally interrogating previously inaccessible windows of human early peri- and post-implantation development.
2023-08-16 | GSE240973 | GEO
Project description:Our ability to study early human post-implantation development remains highly limited due to the ethical and technical challenges associated with intrauterine development of the human embryo after implantation. Despite the great progress made on human blastoids or gastruloids, such elegant models do not constitute an integrated synthetic stem cell-derived embryoid models (SEMs) that includes all the key extra-embryonic tissues of the early pre-gastrulating implanted human conceptus (e.g. hypoblast, yolk-sac, trophoblasts, amnion and extraembryonic mesoderm), and thus, do not recapitulate post-implantation epiblast development within the context of these extra-embryonic compartments. Mouse naïve pluripotent stem cells (PSCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse SEMs, while bypassing the blastocyst-like stage, and eventually initiating organogenesis ex utero. Here, we implement critical adaptations to extend these finding in humans, using only genetically unmodified human naïve PSCs, circumventing the need for ectopic expression of lineage promoting transgenes. Such integrated human SEMs recapitulate all known compartments of early post-implantation stage human embryos, including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity and a connective stalk. This new platform constitutes a tractable stem cell-based model for experimentally interrogating previously inaccessible windows of human early peri- and post-implantation development.
2023-08-21 | GSE241348 | GEO
Project description:Our ability to study early human post-implantation development remains highly limited due to the ethical and technical challenges associated with intrauterine development of the human embryo after implantation. Despite the great progress made on human blastoids or gastruloids, such elegant models do not constitute an integrated synthetic stem cell-derived embryoid models (SEMs) that includes all the key extra-embryonic tissues of the early pre-gastrulating implanted human conceptus (e.g. hypoblast, yolk-sac, trophoblasts, amnion and extraembryonic mesoderm), and thus, do not recapitulate post-implantation epiblast development within the context of these extra-embryonic compartments. Mouse naïve pluripotent stem cells (PSCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse SEMs, while bypassing the blastocyst-like stage, and eventually initiating organogenesis ex utero. Here, we implement critical adaptations to extend these finding in humans, using only genetically unmodified human naïve PSCs, circumventing the need for ectopic expression of lineage promoting transgenes. Such integrated human SEMs recapitulate all known compartments of early post-implantation stage human embryos, including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity and a connective stalk. This new platform constitutes a tractable stem cell-based model for experimentally interrogating previously inaccessible windows of human early peri- and post-implantation development.
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Project description:Our ability to study early human post-implantation development remains highly limited due to the ethical and technical challenges associated with intrauterine development of the human embryo after implantation. Despite the great progress made on human blastoids or gastruloids, such elegant models do not constitute an integrated synthetic stem cell-derived embryoid models (SEMs) that includes all the key extra-embryonic tissues of the early pre-gastrulating implanted human conceptus (e.g. hypoblast, yolk-sac, trophoblasts, amnion and extraembryonic mesoderm), and thus, do not recapitulate post-implantation epiblast development within the context of these extra-embryonic compartments. Mouse naïve pluripotent stem cells (PSCs) have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation mouse SEMs, while bypassing the blastocyst-like stage, and eventually initiating organogenesis ex utero. Here, we implement critical adaptations to extend these finding in humans, using only genetically unmodified human naïve PSCs, circumventing the need for ectopic expression of lineage promoting transgenes. Such integrated human SEMs recapitulate all known compartments of early post-implantation stage human embryos, including epiblast, hypoblast, extra-embryonic mesoderm, and trophoblast surrounding the latter layers. The organized human SEMs recapitulate key hallmarks of post-implantation stage embryogenesis up to 13-14 days post-fertilization (dpf, Carnegie stage 6a), such as bilaminar disk formation, epiblast lumenogenesis, amniogenesis, anterior-posterior symmetry breaking, PGC specification, primary and secondary yolk sac formation, and extra-embryonic mesoderm expansion that defines a chorionic cavity and a connective stalk. This new platform constitutes a tractable stem cell-based model for experimentally interrogating previously inaccessible windows of human early peri- and post-implantation development.
2023-08-16 | GSE229578 | GEO