Employing totipotent cells to reconstruct embryogenesis
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ABSTRACT:
PROVIDER: PRJNA973624 | ENA |
REPOSITORIES: ENA
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Project description:Employing totipotent cells to reconstruct embryogenesis [scRNA-seq]
| PRJNA973633 | ENA
Project description:Employing totipotent cells to reconstruct embryogenesis [RNA-seq]
| PRJNA973069 | ENA
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: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
Project description:During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula. Analysis of Nodal signaling mutants revealed that their transcriptomes were canalized into a subset of wild-type transcriptional trajectories. Some wild-type developmental branchpoints contained cells expressing genes characteristic of multiple fates. These cells appeared to trans-specify from one fate to another. These findings reconstruct the transcriptional trajectories of a vertebrate embryo, highlight the concurrent canalization and plasticity of embryonic specification, and provide a framework to reconstruct complex developmental trees from single-cell transcriptomes. This SuperSeries is composed of the SubSeries listed below.
2018-04-27 | GSE106587 | GEO
Project description:Since the establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable to in vivo blastomeres with embryonic and extraembryonic developmental potency is unviable. Spliceosomes are responsible for mRNA splicing and maturation. Here, we report that spliceosomal repression in mouse ESCs drives pluripotent-to-totipotent state transition. Using the splicing inhibitor Pladienolide B, we realize in vitro culturing of totipotent ESCs comparable to 2- and 4-cell blastomeres at molecular levels for long-time passages, which are therefore termed as totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combined with single-cell RNA-seq technology demonstrate that TBLCs own a robust bidirectional development capability to generate multiple embryonic and extraembryonic cell lineages. Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotent genes, whereas the totipotent genes featured with few short introns are efficiently spliced and transcriptionally activated. Our study provides a principle for capturing and maintenance of totipotent stem cells.
2021-05-15 | GSE168728 | GEO
Project description:We demonstrate induction and long-term maintenance of totipotent stem cells (TotiSCs) from mouse pluripotent stem cells (PSCs) by a combination of three small molecules, TTNPB, 1-Azakenpaullone, and WS6. These cells, which we designated as ciTotiSCs (chemically induced totipotent stem cells), resembled mouse totipotent 2C-embryo stage cells at both transcriptome and epigenome level.
2022-05-25 | GSE185004 | GEO