Highly efficient generation of blastocyst-like structures from mouse totipotent blastomere-like cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA812035 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18208275_1.fastq.gz | Fastqsanger.gz | |||
| SRR18208275_2.fastq.gz | Fastqsanger.gz | |||
| SRR18208276_1.fastq.gz | Fastqsanger.gz | |||
| SRR18208276_2.fastq.gz | Fastqsanger.gz | |||
| SRR18208277_1.fastq.gz | Fastqsanger.gz |
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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:During development, totipotent blastomeres initiate the first cell fate decision to generate inner cell mass and trophectoderm. The trophectoderm forms the placenta mediating fetal-maternal communications, while placental deficiencies cause infertility and pregnancy disorders in humans. However, in vitro systems remodeling the step-wise placental development, particularly encompassing the pre-implantation phase, are still unavailable. Here, using mouse totipotent blastomere-like cells (TBLCs), we successfully realize inducing and long-term maintaining trophectoderm-like stem cells (TELSCs), and further generating placental trophoblast organoids. Interestingly, an intermediate morula trophectoderm-like cells (TELCs) were transiently induced from TBLCs, and quickly converted into TELSCs assembling blastocyst trophectoderm. In 3D culturing condition, TELSCs can form rosette-like structures at peri-implantation period, to eventually generate trophoblast organoids, in which trophoblast progenitors/giant cells, spongiotrophoblasts and syncytiotrophoblasts were all identified at the single-cell level. Transcriptomic and epigenomic analyses enable tracing the step-by-step transition from TBLCs to mature trophoblast lineages. Thus, this study provides a comprehensive differentiation system to understand and investigate placental development.
2025-01-01 | GSE251984 | GEO
Project description:During development, totipotent blastomeres initiate the first cell fate decision to generate inner cell mass and trophectoderm. The trophectoderm forms the placenta mediating fetal-maternal communications, while placental deficiencies cause infertility and pregnancy disorders in humans. However, in vitro systems remodeling the step-wise placental development, particularly encompassing the pre-implantation phase, are still unavailable. Here, using mouse totipotent blastomere-like cells (TBLCs), we successfully realize inducing and long-term maintaining trophectoderm-like stem cells (TELSCs), and further generating placental trophoblast organoids. Interestingly, an intermediate morula trophectoderm-like cells (TELCs) were transiently induced from TBLCs, and quickly converted into TELSCs assembling blastocyst trophectoderm. In 3D culturing condition, TELSCs can form rosette-like structures at peri-implantation period, to eventually generate trophoblast organoids, in which trophoblast progenitors/giant cells, spongiotrophoblasts and syncytiotrophoblasts were all identified at the single-cell level. Transcriptomic and epigenomic analyses enable tracing the step-by-step transition from TBLCs to mature trophoblast lineages. Thus, this study provides a comprehensive differentiation system to understand and investigate placental development.
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Project description:During development, totipotent blastomeres initiate the first cell fate decision to generate inner cell mass and trophectoderm. The trophectoderm forms the placenta mediating fetal-maternal communications, while placental deficiencies cause infertility and pregnancy disorders in humans. However, in vitro systems remodeling the step-wise placental development, particularly encompassing the pre-implantation phase, are still unavailable. Here, using mouse totipotent blastomere-like cells (TBLCs), we successfully realize inducing and long-term maintaining trophectoderm-like stem cells (TELSCs), and further generating placental trophoblast organoids. Interestingly, an intermediate morula trophectoderm-like cells (TELCs) were transiently induced from TBLCs, and quickly converted into TELSCs assembling blastocyst trophectoderm. In 3D culturing condition, TELSCs can form rosette-like structures at peri-implantation period, to eventually generate trophoblast organoids, in which trophoblast progenitors/giant cells, spongiotrophoblasts and syncytiotrophoblasts were all identified at the single-cell level. Transcriptomic and epigenomic analyses enable tracing the step-by-step transition from TBLCs to mature trophoblast lineages. Thus, this study provides a comprehensive differentiation system to understand and investigate placental development.
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Project description:During development, totipotent blastomeres initiate the first cell fate decision to generate inner cell mass and trophectoderm. The trophectoderm forms the placenta mediating fetal-maternal communications, while placental deficiencies cause infertility and pregnancy disorders in humans. However, in vitro systems remodeling the step-wise placental development, particularly encompassing the pre-implantation phase, are still unavailable. Here, using mouse totipotent blastomere-like cells (TBLCs), we successfully realize inducing and long-term maintaining trophectoderm-like stem cells (TELSCs), and further generating placental trophoblast organoids. Interestingly, an intermediate morula trophectoderm-like cells (TELCs) were transiently induced from TBLCs, and quickly converted into TELSCs assembling blastocyst trophectoderm. In 3D culturing condition, TELSCs can form rosette-like structures at peri-implantation period, to eventually generate trophoblast organoids, in which trophoblast progenitors/giant cells, spongiotrophoblasts and syncytiotrophoblasts were all identified at the single-cell level. Transcriptomic and epigenomic analyses enable tracing the step-by-step transition from TBLCs to mature trophoblast lineages. Thus, this study provides a comprehensive differentiation system to understand and investigate placental development.
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Project description:During development, totipotent blastomeres initiate the first cell fate decision to generate inner cell mass and trophectoderm. The trophectoderm forms the placenta mediating fetal-maternal communications, while placental deficiencies cause infertility and pregnancy disorders in humans. However, in vitro systems remodeling the step-wise placental development, particularly encompassing the pre-implantation phase, are still unavailable. Here, using mouse totipotent blastomere-like cells (TBLCs), we successfully realize inducing and long-term maintaining trophectoderm-like stem cells (TELSCs), and further generating placental trophoblast organoids. Interestingly, an intermediate morula trophectoderm-like cells (TELCs) were transiently induced from TBLCs, and quickly converted into TELSCs assembling blastocyst trophectoderm. In 3D culturing condition, TELSCs can form rosette-like structures at peri-implantation period, to eventually generate trophoblast organoids, in which trophoblast progenitors/giant cells, spongiotrophoblasts and syncytiotrophoblasts were all identified at the single-cell level. Transcriptomic and epigenomic analyses enable tracing the step-by-step transition from TBLCs to mature trophoblast lineages. Thus, this study provides a comprehensive differentiation system to understand and investigate placental development.
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Project description:A single mouse blastomere from until 8-cell embryo can generate an entire blastocyst. Whether blastomere-like extended pluripotent stem cells (EPS cells) retain a similar generative capacity remains unknown. Here, we established a 3D differentiation system that enabled the generation of blastocyst-like structures from EPS cells (EPS-blastoids) through lineage segregation and self-organization. EPS-blastoids resembled blastocysts in morphology and cell lineage allocation. EPS-blastoids formation recapitulated key morphogenetic events during preimplantation and early postimplantation development in vitro. Upon transfer, some EPS-blastoids underwent implantation, induced decidualization, and generated live, albeit disorganized, tissues in utero. Single cell and bulk RNA-sequencing analysis revealed that EPS-blastoids contained all three blastocyst cell lineages and shared transcriptional similarity with natural blastocysts. We also provide proof-of-concept that EPS-blastoids can be generated from somatic cells via cellular reprograming. EPS-blastoids provide a unique platform for studying early embryogenesis, and pave the way to generate viable synthetic embryos using cultured cells.
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Project description:A single mouse blastomere from until 8-cell embryo can generate an entire blastocyst. Whether blastomere-like extended pluripotent stem cells (EPS cells) retain a similar generative capacity remains unknown. Here, we established a 3D differentiation system that enabled the generation of blastocyst-like structures from EPS cells (EPS-blastoids) through lineage segregation and self-organization. EPS-blastoids resembled blastocysts in morphology and cell lineage allocation. EPS-blastoids formation recapitulated key morphogenetic events during preimplantation and early postimplantation development in vitro. Upon transfer, some EPS-blastoids underwent implantation, induced decidualization, and generated live, albeit disorganized, tissues in utero. Single cell and bulk RNA-sequencing analysis revealed that EPS-blastoids contained all three blastocyst cell lineages and shared transcriptional similarity with natural blastocysts. We also provide proof-of-concept that EPS-blastoids can be generated from somatic cells via cellular reprograming. EPS-blastoids provide a unique platform for studying early embryogenesis, and pave the way to generate viable synthetic embryos using cultured cells.
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