XEN state reprogramming into self-organizing trophectoderm-like cells enables the assembly of synthetic embryoids
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE159883 | GEO | 2022/09/13
REPOSITORIES: GEO
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Project description:The conventional trophoblast stem cells represent post-implantation extraembryonic ectoderm-like state and not that of pre-implantation trophectoderm, irrespective of their origin. To capture the trophectoderm-like state we established culture conditions that facilitate the co-existence of characteristics of both the extraembryonic lineages, namely, primitive endoderm and trophectoderm. We term these cells XTE cells. We carried out RNA-seq on XTE cells from different origins, as well as XEN cells, XEN-like cells, and ES cells, to assess their transcriptional profiles and identify putative marker genes and master regulators.
2022-09-13 | E-MTAB-8788 | biostudies-arrayexpress
Project description:The implantation process begins with attachment of the trophectoderm (TE) of the blastocyst to the maternal endometrial epithelium. Herein we have investigated the transcriptome of mural TE cells from 13 human blastocysts and compared these with those of human embryonic stem cell (hESC)-derived-TE (hESCtroph). The transcriptomes of hESFtroph at days 8, 10, and 12 had the greatest consistency with TE. Among genes coding for secreted proteins of the TE of human blastocysts and of hESCtroph are several molecules known to be involved in the implantation process as well as novel ones, such as CXCL12, HBEGF, inhibin A, DKK3, Wnt 5A, follistatin. The similarities between the two lineages underscore some of the known mechanisms and offer discovery of new mechanisms and players in the process of the very early stages of human implantation. We propose that the hESCtroph is a viable functional model of human trophoblasts to study trophoblast-endometrial interactions. Furthermore, the data derived herein offer the promise of novel diagnostics and therapeutics aimed at practical challenges in human infertility and pregnancy disorders associated with abnormal embryonic implantation. Transcriptome analyses suggest human embryonic stem cell-derived-trophoblast as a viable functional model of human trophoblast to study trophoblast-endometrial interactions. Five pools of trophectoderm cells were subjected to RNA isolation and microarray. The resulting data were compared to the transcriptomes of H7 human embryonic stem cells differentiated to the trophoblast lineage after 0, 2, 4, 6, 8, 10 and 12 days of induction with BMP-4. This submission represents the trophectoderm cells from blastocysts.
2011-09-08 | E-GEOD-30650 | biostudies-arrayexpress
Project description:Transcriptome at the single-cell level of a human embryoid model, which recapitulates aspects of lineage diversification and three-dimensional tissue architecture of the human embryo from the implantation to the onset of gastrulation, was profiled at different time points. Similarly, chimpanzee embryoids were generated and profiled to reveal transcriptome dynamics during the early post-implantation chimpanzee development. Our comparative transcriptome analyses reveal a critical role of NODAL signaling in human mesoderm specification, which is functionally validated by generating embryoids with NODAL-knockout (KO) hPSCs.
2021-10-13 | GSE185643 | GEO
Project description:In humans, the embryonic genome activation (EGA) program is functional by day 3 after fertilization. The 6-8 cell stage embryo (day 3 post-fertilization) starts the process of “compaction” that leads to the generation of the tightly organized cell mass of the morula and is followed by differentiation of the morula into a blastocyst. The transition from day 3 embryos to day 5 blastocysts is likely to be controlled by many and specific changes in the expression of different genes. We used mRNA amplification technique and compared the transcriptomes of day 3 human embryos and trophectoderm (TE) cells from day 5 human blastocysts to identify transcripts that are differentially expressed during the embryo-to-TE transition and involved in the TE specification. These six embryo samples were compared to our five human trophectoderm samples that are available in GEO under the following accession numbers: GSM706168 GSM706169 GSM706170 GSM706171 GSM706172
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Project description:Single-cell RNA sequencing data of stem cell-derived microfluidic human embryoids, NODAL-KO human embryoids and chimpanzee embryoids
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Project description:Aneuploidy has been well documented in blastocyst embryos, but prior studies have been limited in scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening (PGS) in a 24-hour protocol. The method diagnoses chromosome copy number, structural chromosome aberrations, parental source of aneuploidy, and distinguishes certain meiotic from mitotic errors. In this study our objective was to examine aneuploidy in human blastocysts and determine correspondence of karyotypes between trophectoderm (TE) and inner cell mass (ICM). We disaggregated 51 blastocysts from seventeen couples into ICM and one or two TE fractions. The average maternal age was 31. Next, we ran 24-chromosome microarray molecular karyotyping on all of the samples, and then performed a retrospective analysis of the data. The average per-chromosome confidence was 99.95%. Approximately 80% of blastocysts were euploid. The majority of aneuploid embryos were simple aneuploid, i.e., one or two whole-chromosome imbalances. Structural chromosome aberrations, which are common in cleavage stage embryos, occurred in only three blastocysts (5.8%). All TE biopsies derived from the same embryos were concordant. Forty-nine of fifty-one (96.1%) inner cell mass (ICM) samples were concordant with TE biopsies derived from the same embryos. Discordance between TE and ICM occurred only in the two embryos with structural chromosome aberration. We conclude that trophectoderm karyotype is an excellent predictor of inner cell mass karyotype. Discordance between TE and ICM occurred only in embryos with structural chromosome aberrations.
2010-09-28 | GSE22864 | GEO
Project description:Classical mouse embryology has established a paradigm of early development drivenby sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derivedfrom early epiblast have lost the potency to produce extraembryonic trophectoderm.We show in contrast that human naive epiblast cells readily make trophectoderm.Inhibition of ERK signalling, instrumental in naive stem cell propagation, unexpectedlypotentiates trophectoderm formation, an effect enhanced by Nodal inhibition.Transcriptome analyses authenticate conversion into trophectoderm with subsequentproduction of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Geneticperturbations indicate that NANOG suppresses and TFAP2C enables trophectoderminduction. Consistent with post-implantation progression, trophectoderm potential isextinguished in conventional human pluripotent stem cells, which instead makeamnion. Finally, human embryo epiblasts from late blastocysts efficiently generatetrophectoderm and differentiated trophoblast. Thus, pluripotent cells in the humanembryo retain extraembryonic lineage plasticity and regenerative potential untilimplantation. Harnessing this unanticipated regulative capacity may be beneficial forassisted reproduction technology.
2021-02-09 | GSE166401 | GEO
Project description:Classical mouse embryology has established a paradigm of early development drivenby sequential lineage bifurcations. Accordingly, mouse embryonic stem cells derivedfrom early epiblast have lost the potency to produce extraembryonic trophectoderm.We show in contrast that human naive epiblast cells readily make trophectoderm.Inhibition of ERK signalling, instrumental in naive stem cell propagation, unexpectedlypotentiates trophectoderm formation, an effect enhanced by Nodal inhibition.Transcriptome analyses authenticate conversion into trophectoderm with subsequentproduction of syncitiotrophoblast, cytotrophoblast and trophoblast stem cells. Geneticperturbations indicate that NANOG suppresses and TFAP2C enables trophectoderminduction. Consistent with post-implantation progression, trophectoderm potential isextinguished in conventional human pluripotent stem cells, which instead makeamnion. Finally, human embryo epiblasts from late blastocysts efficiently generatetrophectoderm and differentiated trophoblast. Thus, pluripotent cells in the humanembryo retain extraembryonic lineage plasticity and regenerative potential untilimplantation. Harnessing this unanticipated regulative capacity may be beneficial forassisted reproduction technology.
2021-02-10 | GSE166422 | GEO
Project description:The murine embryonic–trophoblast–extra-embryonic endoderm (ETX) model is an integrated stem cell–based model to study early postimplantation development. It is based on the self-assembly potential of embryonic, trophoblast, and hypoblast/primitive/visceral endoderm-type stem cell lines (ESC, TSC, and XEN, respectively) to arrange into postimplantation egg cylinder–like embryoids. Here, we provide an optimized method for reliable and efficient generation of ETX embryoids that develop into late gastrulation in static culture conditions. It is based on transgenic Gata6-overproducing ESCs and modified assembly and culture conditions. Using this method, up to 43% of assembled ETX embryoids exhibited a correct spatial distribution of the three stem cell derivatives at day 4 of culture. Of those, 40% progressed into ETX embryoids that both transcriptionally and morphologically faithfully mimicked in vivo postimplantation mouse development between E5.5 and E7.5. The ETX model system offers the opportunity to study the murine postimplantation egg cylinder stages and could serve as a source of various cell lineage precursors.
2023-01-25 | GSE206132 | GEO
Project description:The trophoblast cell lineage is specified as early as the blastocyst stage, leading to the individualization of trophectoderm from pluripotent cells of the inner cell mass. We used a double in vitro transcription mRNA amplification technique and compared trophectoderm with pluripotent stem cells.
2011-07-15 | GSE28504 | GEO