Employing totipotent cells to reconstruct embryogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA973624 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24601528_1.fastq.gz | Fastqsanger.gz | |||
| SRR24601528_2.fastq.gz | Fastqsanger.gz | |||
| SRR24601529_1.fastq.gz | Fastqsanger.gz | |||
| SRR24601529_2.fastq.gz | Fastqsanger.gz | |||
| SRR24601530_1.fastq.gz | Fastqsanger.gz |
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Project description:Employing totipotent cells to reconstruct embryogenesis [RNA-seq]
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Project description:Employing totipotent cells to reconstruct embryogenesis [scRNA-seq]
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Project description:Blastoids, a structure similar to blastocysts in morphological and molecular level, can be applied to regeneration research. Using totipotent cells to construct blastoids will extend the information of early development to an earlier stage, and explore clues of regeneration. Totipotent blastomere-like cells (TBLCs) are a novel type of stably cultured mouse totipotent cell line generated by inhibiting spliceosomes. Here, we constructed blastoids (TBL-blastoids) in a new three-dimensional culture system using TBLCs. Morphological and transcriptomic analysis revealed TBL-blastoids contained typical morphology and key cell lineages of blastocysts and had higher degree of consistency in developmental rate and morphology compared to other blastoids. Moreover, TBL-blastoids implanted into uterus, induced decidua and even developed to embryonic tissues, indicating their in vivo developmental potential. The expansion and structures of TBL-blastoids in the IVC system also showed their in vitro developmental potential. The efficiency of generating TBL-blastoids and implantation rate suggest the necessity of TE-like component formation. Meanwhile, TBLCs can differentiate into extraembryonic cell lines directly, which provides an alternative strategy for evaluating totipotency. Furthermore, we explored the impacts of senescence, a central role in regeneration, on TBLCs and found that cellular senescence impaired the totipotency of TBLCs and the efficiency of generating blastoids. Also, the in vivo and in vitro developmental potential of TBL-blastoids were declined. In conclusion, the induction of TBLCs into blastoids and extraembryonic cells is valuable for promoting regeneration, early embryonic development study and evaluating totipotency.
2024-03-05 | GSE232715 | GEO
Project description:Blastoids, a structure similar to blastocysts in morphological and molecular level, can be applied to regeneration research. Using totipotent cells to construct blastoids will extend the information of early development to an earlier stage, and explore clues of regeneration. Totipotent blastomere-like cells (TBLCs) are a novel type of stably cultured mouse totipotent cell line generated by inhibiting spliceosomes. Here, we constructed blastoids (TBL-blastoids) in a new three-dimensional culture system using TBLCs. Morphological and transcriptomic analysis revealed TBL-blastoids contained typical morphology and key cell lineages of blastocysts and had higher degree of consistency in developmental rate and morphology compared to other blastoids. Moreover, TBL-blastoids implanted into uterus, induced decidua and even developed to embryonic tissues, indicating their in vivo developmental potential. The expansion and structures of TBL-blastoids in the IVC system also showed their in vitro developmental potential. The efficiency of generating TBL-blastoids and implantation rate suggest the necessity of TE-like component formation. Meanwhile, TBLCs can differentiate into extraembryonic cell lines directly, which provides an alternative strategy for evaluating totipotency. Furthermore, we explored the impacts of senescence, a central role in regeneration, on TBLCs and found that cellular senescence impaired the totipotency of TBLCs and the efficiency of generating blastoids. Also, the in vivo and in vitro developmental potential of TBL-blastoids were declined. In conclusion, the induction of TBLCs into blastoids and extraembryonic cells is valuable for promoting regeneration, early embryonic development study and evaluating totipotency.
2024-03-05 | GSE232634 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-05 | GSE232718 | GEO
Project description:Mammalian embryogenesis begins with a totipotent zygote. Early embryogenesis can be recapitulated by aggregated extended pluripotent stem cells (EPSCs) in a 3D culture system. However, the efficiency of generating blastoids is low and whether other reported totipotent stem cells retained a similar capacity remains unknown. Here we show that spliceosomal repressed totipotent blastomere-like cells (TBLCs) form blastocyst-like structures when aggregated in 3D microwells with around 80% efficiency. TBLC-blastoids resemble blastocysts in morphology and cell-lineage allocation, show similar transcriptional profile with natural blastocysts and contain more TE cells and fewer undefined intermediate cells compared to blastoids from EPSCs. Moreover, TBLC-blastoids can develop beyond the implantation stage in vitro and induce decidualization after transferred into uterus. In summary, we supply an alternative cell type to generate ameliorated blastoids highly efficiently for studying early mouse embryogenesis.
2022-11-08 | GSE197779 | GEO
Project description:The development of stem-cell-derived models of mammalian embryogenesis has provided invaluable tools for investigating embryo development. However, constructing embryo models that can continuously recapitulate the full developmental trajectory, from zygotic genome activation (ZGA) to gastrulation, remains a major challenge. Here, we developed a new chemical cocktail to induce totipotent-like cells with robust proliferation ability, and leveraged these cells to establish a stepwise protocol to generate a continuous embryo model. This model sequentially mimics mouse embryogenesis from embryonic day 1.5 to 7.5. It recapitulates key developmental milestones, including ZGA in 2-cell embryos, the diversification of embryonic and extraembryonic lineages from 4-cell to 64-cell stages, the formation of blastocysts, and the subsequent development into post-implantation egg cylinders. Notably, these structures can undergo gastrulation, as evidenced by primitive streak formation and the subsequent emergence of several hallmarks of early organogenesis. Our study opens new avenues for modeling mammalian embryogenesis in vitro.
2025-09-18 | GSE287909 | GEO
Project description:The development of stem-cell-derived models of mammalian embryogenesis has provided invaluable tools for investigating embryo development. However, constructing embryo models that can continuously recapitulate the full developmental trajectory, from zygotic genome activation (ZGA) to gastrulation, remains a major challenge. Here, we developed a new chemical cocktail to induce totipotent-like cells with robust proliferation ability, and leveraged these cells to establish a stepwise protocol to generate a continuous embryo model. This model sequentially mimics mouse embryogenesis from embryonic day 1.5 to 7.5. It recapitulates key developmental milestones, including ZGA in 2-cell embryos, the diversification of embryonic and extraembryonic lineages from 4-cell to 64-cell stages, the formation of blastocysts, and the subsequent development into post-implantation egg cylinders. Notably, these structures can undergo gastrulation, as evidenced by primitive streak formation and the subsequent emergence of several hallmarks of early organogenesis. Our study opens new avenues for modeling mammalian embryogenesis in vitro.
2025-09-18 | GSE287908 | GEO
Project description:Epigenetic remodeling following fertilization is essential for the acquisition of embryonic totipotency. The role of H4K20me3, a key component epigenetic mark, remains largely unexplored in the context of early human embryogenesis. Here, we observed a dynamic erasure of H4K20me3 modification during zygotic genome activation (ZGA), followed by a re-establishment after ZGA in human embryos. Using in vitro reprogramming of totipotent-like states, we demonstrated transient removal of H4K20me3 in human embryonic stem cells (hESCs) promotes DUX4-mediated expression of totipotent genes, the transition into a totipotent-like state.
2025-05-31 | GSE287564 | GEO
Project description:Cell signaling induced cell fate determination is central to stem cell and developmental biology. Embryonic stem cells (ESC) are an attractive model for understanding the relationship between cell signaling and cell fates. Cultured mouse ESCs can exist in multiple cell states resembling distinct stages of early embryogenesis, such as Totipotent, Pluripotent, Primed and Primitive Endoderm. The signaling mechanisms regulating the Totipotent state acquisition and coexistence of these states are poorly understood. Here we identify BMP4 as an inducer of the Totipotent state. However, we discovered that BMP4-mediated induction of the Totipotent state is constrained by the cross-activation of FGF, TGF- and WNT pathways. We exploited this finding to enhance the proportion of Totipotent cells in ESCs by rationally inhibiting these cross-activated pathways using small molecules. Single-cell mRNA-sequencing further revealed that induction of the Totipotent state is accompanied by the suppression of both the Primed and Primitive Endoderm states. Furthermore, the reprogrammed Totipotent cells generated in culture have a molecular and functional resemblance to Totipotent cell stages of preimplantation embryos. Our findings reveal a novel BMP4 signaling mechanism in ESCs to regulate multiple cell states, potentially significant for managing stem cell heterogeneity in differentiation and reprogramming.
2023-06-26 | GSE198384 | GEO