Similar Datasets
Project description:The embryo instructs the allocation of cell states to spatially regulate growth and functions. In the blastocyst, the formation and divergence of the trophoblast lineage ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the inner epiblast cells (inducers) that captures stable, highly self-renewing, pre-implantation-like mouse trophectoderm stem cells (TESCs). When exposed to suboptimal inducers, these stem cells form interconvertible subpopulations with reduced self-renewal, known as trophoblast stem cells (TSCs), and resembling peri-implantation progenitors. TECSs have an enhanced capacity to form blastoids that implant more efficiently in utero. We find that this enhanced capacity is due to epiblast inducers not only controlling trophoblast growth but also trophoblast secretion of WNT6/7B that stimulates uterine decidualization. Thus, the embryo leverages epiblast inductions to drive both the growth and decidualization potential of trophoblasts required for implantation and development.
2022-06-07 | GSE200958 | GEO
Project description:The embryo instructs the allocation of cell states to spatially regulate growth and functions. In the blastocyst, the formation and divergence of the trophoblast lineage ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the inner epiblast cells (inducers) that captures stable, highly self-renewing, pre-implantation-like mouse trophectoderm stem cells (TESCs). When exposed to suboptimal inducers, these stem cells form interconvertible subpopulations with reduced self-renewal, known as trophoblast stem cells (TSCs), and resembling peri-implantation progenitors. TECSs have an enhanced capacity to form blastoids that implant more efficiently in utero. We find that this enhanced capacity is due to epiblast inducers not only controlling trophoblast growth but also trophoblast secretion of WNT6/7B that stimulates uterine decidualization. Thus, the embryo leverages epiblast inductions to drive both the growth and decidualization potential of trophoblasts required for implantation and development.
2022-06-07 | GSE200960 | GEO
Project description:Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero.
| PRJNA827763 | ENA
Project description:Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [scRNAseq]
| PRJNA827775 | ENA
Project description:Epiblast inducers capture mouse Trophectoderm Stem Cells in vitro and pattern blastoids for implantation in utero. [bulk RNA-Seq]
| PRJNA827773 | ENA
Project description:Implantation is a hallmark of mammalian embryogenesis during which embryos establish their contacts with the maternal endometrium, remodel, and undertake growth and differentiation. The mechanisms and sequence of events through which embryos change their shape during this transition are largely unexplored. Here, we show that the first extraembryonic lineage, the polar trophectoderm, is the key regulator for remodeling the embryonic epiblast. Loss of its function after immuno-surgery or inhibitor treatments prevents the epiblast shape transitions. In the mouse, the polar trophectoderm exerts physical force upon the epiblast, causing it to transform from an oval into a cup shape. In human embryos, the polar trophectoderm behaves in the opposite manner, exerting a stretching force. By mimicking this stretching behavior in mouse embryogenesis, we could direct the epiblast to adopt the disc-like shape characteristic of human embryos at this stage. Thus, the polar trophectoderm acts as a conserved regulator of epiblast shape.
| S-EPMC7816124 | biostudies-literature
Project description:Understanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast, trophectoderm and primitive endoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a "cup". Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG# (MechanoGenetic Sharp), an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is essential to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed can dictate the cup shape of the epiblast and fosters its movement towards the uterine tissue. Our results offer novel mechanical insights into mouse peri-implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.
| S-EPMC8318228 | biostudies-literature
Project description:One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2 and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.
| S-EPMC8791832 | biostudies-literature
Project description:The pluripotent state, which is first established in the primitive ectoderm cells of blastocysts, is lost progressively and irreversibly during subsequent development. For example, development of post-implantation epiblast cells from primitive ectoderm involves significant transcriptional and epigenetic changes, including DNA methylation and X chromosome inactivation, which create a robust epigenetic barrier and prevent their reversion to a primitive-ectoderm-like state. Epiblast cells are refractory to leukaemia inhibitory factor (LIF)-STAT3 signalling, but they respond to activin/basic fibroblast growth factor to form self-renewing epiblast stem cells (EpiSCs), which exhibit essential properties of epiblast cells and that differ from embryonic stem (ES) cells derived from primitive ectoderm. Here we show reprogramming of advanced epiblast cells from embryonic day 5.5-7.5 mouse embryos with uniform expression of N-cadherin and inactive X chromosome to ES-cell-like cells (rESCs) in response to LIF-STAT3 signalling. Cultured epiblast cells overcome the epigenetic barrier progressively as they proceed with the erasure of key properties of epiblast cells, resulting in DNA demethylation, X reactivation and expression of E-cadherin. The accompanying changes in the transcriptome result in a loss of phenotypic and epigenetic memory of epiblast cells. Using this approach, we report reversion of established EpiSCs to rESCs. Moreover, unlike epiblast and EpiSCs, rESCs contribute to somatic tissues and germ cells in chimaeras. Further studies may reveal how signalling-induced epigenetic reprogramming may promote reacquisition of pluripotency.
| S-EPMC3863718 | biostudies-literature
Project description:Recently, a new wave of synthetic embryo systems (SESs) has been established from cultured cells for efficient and ethical embryonic development research. We recently reported our epiblast stem cell (EPISC) reprogramming SES that generates numerous blastocyst (BC)-like hemispheres (BCLH) with pluripotent and extraembryonic cell features detected by microscopy. Here, we further explored the system over key time points with single-cell RNA-sequencing analysis. We found broad induction of the 2C-like reporter MERVL and RNA velocities diverging to three major cell populations with gene expression profiles resembling those of pluripotent epiblast, primitive endoderm, and trophectoderm. Enrichment of those three induced BC-like cell fates involved key gene-regulatory networks, zygotic genome activation-related genes, and specific RNA splicing, and many cells closely resembled in silico models. This analysis confirms the induction of extraembryonic cell populations during EPISC reprogramming. We anticipate that our unique BCLH SES and rich dataset may uncover new facets of cell potency, improve developmental biology, and advance biomedicine.
| S-EPMC8185450 | biostudies-literature