A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naive PSCs (scRNA-Seq I)
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PROVIDER: PRJNA955027 | ENA |
REPOSITORIES: ENA
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Project description:A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naïve PSCs
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Project description:A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naïve PSCs (Multiome ATAC-Seq)
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Project description:A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naïve PSCs (scRNA-Seq II)
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Project description:A Human Post-Implantation Embryoid Model Derived Ex Utero Solely from Genetically Unmodified Naïve PSCs (Multiome scRNA-Seq)
| PRJNA1001405 | ENA
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
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.
2023-08-16 | GSE239931 | 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.
2023-08-16 | GSE240973 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-08-16 | GSE239932 | GEO
Project description:Different types of in vitro expanded stem cells can contribute to embryonic or extra-embryonic compartments after microinjection into blastocysts. However, whether stem cells could give rise to advanced gastrulating whole embryo-like structures with both embryonic and extra-embryonic compartments, without relying on a micro-injected host embryo, remains to be achieved. Thus far, in vitro aggregated stem cells have failed to generate post-gastrulation embryos ex utero or in utero, which partially resulted from the lack of methods for prolonged expansion of embryos until advanced developmental stages ex utero. Here we adapt recently optimized platform and conditions for ex utero growth of natural embryos, to generate complete mouse synthetic embryos, with both embryonic and extra-embryonic compartments, and by starting solely from naïve ESCs. The latter is achieved following co-aggregating non-transduced naïve ESCs, with Cdx2- and Gata4- transiently pulsed naïve ESCs, to promote their trophoblast and primitive endoderm lineage induction, respectively. The obtained synthetic embryos adequately advance in this platform through developmental milestones and accomplish gastrulation and develop organs progenitors within normally developed extra-embryonic compartments. Our findings highlight the plastic developmental potential of the naïve pluripotent state to functionally self-organize and reconstitute the entire early mammalian embryo.
2022-07-31 | GSE208680 | GEO