Ex utero Mouse Embryogenesis from Pre-Gastrulation to Late-Organogenesis
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PROVIDER: PRJNA628518 | ENA |
REPOSITORIES: ENA
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Project description:Establishment of the mammalian body plan occurs shortly after the embryo implants into the maternal uterus, and our understanding of post-implantation developmental processes remains limited. While methods for in vitro culture of pre- and peri-implantation mouse embryos are routinely utilized, approaches for robust culture of post-implantation embryos from egg cylinder stages until advanced organogenesis remain to be established. We develop herein highly stable ex utero post-implantation mouse embryo culture platforms, that enable appropriate development of embryos before gastrulation (E5.5) until the hind limb formation stage (E11). Late gastrulating embryos (E7.5) are grown in 3D rotating bottles settings, while extended culture from pre-gastrulation stages (E5.5 or E6.5) requires a combination of novel static and rotating bottle culture protocols. Histological, molecular, and single cell RNA-seq analysis validate that the ex utero developed embryos recapitulate precisely in utero development. This culture system is amenable to introducing a variety of embryonic perturbations and micro-manipulations that can be followed ex utero for up to 6 days. Establishment of a system to robustly grow normal mouse embryos ex utero from pre-gastrulation to advanced organogenesis represents a valuable tool to investigate post-implantation embryogenesis, eliminating the uterine barrier to mechanistically interrogate morphogenesis and tissue specification in mammals.
2021-02-15 | GSE149372 | GEO
Project description:Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, non-human primates (NHPs) are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we have collected six Carnegie stage (CS) 8-CS11 cynomolgus monkey embryos and performed in-depth transcriptome analyses of 56,636 single cells. Our analyses reveal transcriptomic features of major peri-gastrulation cell types, which help shed light on morphogenetic events including primitive streak (PS) development, somitogenesis, gut tube formation, neural tube patterning, and neural crest regionalization in primates. In addition, comparative analyses with mouse embryos and human embryoids uncover conserved and divergent features of peri-gastrulation development across species, e.g. species-specific dependency on Hippo signaling during presomitic mesoderm differentiation, and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the NHP research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.
2022-10-26 | GSE193007 | 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
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 | GSE205634 | GEO
Project description:Studies in mouse have led to enormous progress in our understanding of early human development. The identification of genes and the signaling pathways involved in mouse embryogenesis have helped us to better understand fertilization, morulation, gastrulation, organogenesis and embryonic development in mammals. We report a detailed analysis of the global gene expression profiles from oocyte to the end of organogenesis in mouse. Our studies revealed distinct temporal regulation patterns for genes belonging to different functional categories, supporting their roles during organogenesis.
2013-09-11 | GSE39897 | GEO
Project description:Embryo-like structures generated from stem cells can achieve varying developmental milestones, but none have been shown to progress through gastrulation, neurulation, and organogenesis. Here, we show that "ETiX" mouse embryoids, assembled from embryonic stem cells, trophoblast stem cells and inducible extraembryonic endoderm stem cells, can develop into gastrulating embryoids, and beyond to generate neurulating embryoids, which generate the progenitors needed to create the entire organism. The head-folds of ETiX neurulating embryoids show anterior expression of Otx2, defining forebrain and midbrain regions that resemble those of the natural mouse embryo. Neurulating embryoids also develop beating heart-like structures, trunks comprising a neural tube and somites, tail buds containing neuromesodermal progenitors and primordial germ cells, and gut tubes derived from definitive endoderm. Notably, neurulating embryoids also develop a yolk sac with blood islands. Overall, ETiX neurulating embryoid formation strongly resembles natural embryogenesis, advancing embryo-like development further than any other stem-cell derived model and within extra-embryonic membranes.
2022-08-12 | GSE209792 | GEO
Project description:Studies in mouse have led to enormous progress in our understanding of early human development. The identification of genes and the signaling pathways involved in mouse embryogenesis have helped us to better understand fertilization, morulation, gastrulation, organogenesis and embryonic development in mammals. We report a detailed analysis of the global gene expression profiles from oocyte to the end of organogenesis in mouse. Our studies revealed distinct temporal regulation patterns for genes belonging to different functional categories, supporting their roles during organogenesis. Mouse embryos were selected at successive stage for for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of embryos at each developmental stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected embryos according to morphological criteria at 12 time-points from embryos to newborn
2013-09-11 | E-GEOD-39897 | biostudies-arrayexpress
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.
2023-08-16 | 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.
2023-08-21 | GSE241348 | GEO