The chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids.
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ABSTRACT:
PROVIDER: PRJNA532401 | ENA |
REPOSITORIES: ENA
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Project description:The early mammalian conceptus (blastocyst) contains two supporting extraembryonic tissues - the trophectoderm and the primitive endoderm (PrE) - that encase and guide the epiblast (Epi) to eventually form the all body. Modifications of the conceptus exposed key genes regulating these tissues co-development. However, the combination of signalling pathways at play remains elusive. Stem cell-based models including embryoid bodies and blastoids can be generated in large numbers and subjected to high-content screens. Here, we use combinatorial screens of proteins, GPCR ligands and small molecules to rapidly (<96 hours) and efficiently (80%) guide embryoid bodies to form a three dimensional PrE-/Epiblast-like niche in chemically-defined conditions (gel-free, serum-free). This bipotent niche spontaneously progresses, without growth factors, to form a pro-amniotic cavity surrounded by a polarized Epi covered by parietal and visceral endoderm-like cells. In blastoids, these molecules enhance the ratio and number of Gata6+/Nanog+ cells and promote the survival, expansion and morphogenesis of a post-implantation-like Epi in vitro. Altogether, modelling early development in chemically-defined conditions delineates the pathways sufficient to form a functional PrE/Epiblast niche that fuels post-implantation development.
2021-04-01 | GSE129655 | GEO
Project description:About one week after fertilization, human embryos implant into the uterus. This necessitates the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (PXGL hPSCs) efficiently (>70%) form blastoids generating blastocyst-stage analogs of the 3 founding lineages (>97% trophectoderm, epiblast, and primitive endoderm) according to the sequence and to the pace of blastocyst development. Blastoids form the first axis and we observe that the epiblast induces the maturation of the polar trophectoderm that consequently acquires the specific and transient potential to attach to hormonally-stimulated endometrial cells. Such human blastoids are faithful, scalable, versatile, and ethical models to explore human implantation and development.
2021-09-15 | GSE177689 | GEO
Project description:Naïve human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures (“blastoids”) that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick 3D extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day 21. We also show that modulation of WNT signaling alters the balance between epiblast and trophoblast fates in post-implantation blastoids. This work demonstrates that 3D-cultured blastoids offer a continuous and integrated in vitro model system of human embryonic and extraembryonic development from pre-implantation to early gastrulation stages.
2023-09-07 | GSE226794 | GEO
Project description:Shortly after fertilization, human embryos implant into the uterus. This requires the formation of a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Appropriate stem cells can form a blastocyst model, which we termed blastoid. Here we show that naive human pluripotent stem cells (hPSCs) triply inhibited for the Hippo, TGF-β, and ERK pathways consistently and efficiently (>70%) form blastoids that generate transcriptional pre-implantation analogs of the three founding lineages (trophoblast, epiblast, primitive endoderm; >97%) according to the sequence and pace of blastocyst development. Blastoids spontaneously form an axis marked by the maturation of the polar region, which acquires the potential to specifically attach to hormonally stimulated endometrial cells, as during in utero implantation. Such human blastoids are scalable, versatile, and ethical models to explore human implantation and development.
2021-09-15 | GSE179040 | GEO
Project description:The identification of changes in transcriptional regulation during priming and differentiation of embryonic stem (ES) cells towards the endoderm lineage. Specific populations of ES cells, either primed or committed to endoderm, were isolated and subjected to global nuclear run on sequencing (GRO-Seq). The hHex-Venus (HV) reporter ES cell line, HVJu5.1 (Canham et al., 2010) was used to isolate HV- and HV+ ES cells. Primed ES cells were identified based on the expression of the HV marker in addition to the cell surface marker of undifferentiated ES cells, SSEA-1, (the lower and upper 25% of SSEA-1+, HV expressing cells). When challenged to differentiate, HV- ES cells are primed towards an epiblast fate, while HV+ ES cells are primed towards primitive endoderm. However, these populations are considered primed, rather than committed, as they will readily interconvert when re-introduced into standard ES cell culture conditions. ES cells were grown in self-renewing conditions (GMEM, LIF, 10% FCS, plated on gelatin coated dishes). Endoderm was obtained by differentiating ES cells in medium without the cytokine LIF for 5 days. The HV+, SSEA-1- differentiated fraction was then sorted and represents an early stage in endoderm differentiation.
2022-01-03 | GSE58503 | GEO
Project description:The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast, and primitive endoderm (PrE). Although stem cell lines that retain functional properties of epiblasts or trophoblasts have been established, establishment of stem cell
2021-12-31 | GSE159181 | 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 | GSE200958 | GEO
Project description:The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast, and primitive endoderm (PrE). Although stem cell lines that retain functional properties of epiblasts or trophoblasts have been established, establishment of stem cell lines that fully retain developmental potential of PrE has long been awaited. Here we report derivation of primitive endoderm stem (PrES) cells, which are capable to give rise functional PrE derived tissues and support fetal development of PrE-depleted blastocysts in chimeras, in mice.
2021-12-31 | GSE159183 | 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:EpiSCs established from murine epiblast were differentiated to posterior primitive streak (PPS) and analyzed using scRNA-seq to investigate identity and homogeneity of the resulting population.
2022-11-30 | E-MTAB-12106 | biostudies-arrayexpress