Primary specification of blastocyst trophectoderm by scRNA-seq: new insights into embryo implantation
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE133200 | GEO | 2022/08/01
REPOSITORIES: GEO
Similar Datasets
Project description:Implantation is a milestone event during mammalian embryogenesis. Implantation failure is a nonnegligible cause of human early pregnancy loss. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, it remains elusive how the gene regulatory network and epigenetic mechanisms control human embryo implantation. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 8,000 individual cells from 65 human peri-implantation embryos were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast (EPI), primitive endoderm (PE), and trophectoderm (TE) lineages, suggesting robust preparation for the proper establishment of a mother-to-offspring connection during implantation. Female embryos showed initiation of random X chromosome inactivation based on analysis of parental allele-specific expression of X chromosome-linked genes during implantation. Surprisingly, by the single-cell Trio-Seq (scTrio-Seq) analysis, the genome re-methylation of PE lineage was shown to be much slower than those of both EPI and TE lineages during implantation process, indicating distinct DNA methylome re-establishment features between EPI and PE although both of which were derived from inner cell mass (ICM). Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, offering new insights and future efforts in early embryonic development and reproductive medicine.
2019-07-11 | GSE109555 | GEO
Project description:The role of microRNAs (miRNA) in first cell fate choice of the preimplantation mouse embryo remains unresolved, as gene expression and knockout data are conflicting. This cell fate choice generates the extraembryonic lineage of the trophoblast and the embryonic lineage of the epiblast (inner cell mass). The trophoblast differentiates into polar and mural cells, where polar cells contribute to placental development and mural cells to the implantation process and Reichert’s membrane. The inner cell mass further differentiates into the epiblast and primitive endoderm. We used stem cell lines that can be derived from the trophoblast and epiblast lineages to address the role of miRNAs in early lineage cell fate specification and determination. Using embryonic stem cells (ESC) and trophoblast stem cells (TSC) as starting and ending states of cell development we identified a network of TSC expressed miRNAs that are enriched in ESC targets mRNA. We used constitutive and inducible expression of TSC enriched miRNAs in ESC and show that they can drive cell morphology and gene expression profiles similar to trophoblast. Additionally we show that this process required HDAC2 inhibition and is miRNA specific, as cardiac specific miR-1 could not induce trophoblast under these conditions. In contrast to embryo derived and Cdx2 induced trophoblast cells, miRNAs promote a mural TE like cell phenotype. Transplantation into preimplantation mouse embryos showed that miRNA-induced trophoblast preferentially contributes to the mural trophoblast in both the blastocyst and the Reichert’s membrane. Our data support a role for miRNAs and HDACs in the specification of the trophoblast and potentially the polar and mural cell types.
2017-03-01 | GSE79599 | 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
2012-07-08 | E-GEOD-33025 | 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:To determine the effect of Zika virus infection on pre-implantation embryonic development, we performed single blastocyst RNA-Seq on MOCK and ZIKV infected embryos. ZIKV infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the mechanisms underlying fetal loss remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, or pre- and peri-implantation, because most current studies of ZIKV infection in pregnancy models focus on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be efficiently infected with ZIKV, and that trophectoderm can propagate virus causing cell death of neural progenitors. These findings were corroborated by our demonstration that hESC-derived trophectoderm cells are infected by ZIKV in a dose dependent manner. RNAseq of single blastocysts revealed key transcriptional changes in cellular and physiologic functions upon ZIKV infection, including nervous system development and function, prior to commitment to the neural cell lineage. Finally, the pregnancy rate of mice infected pre-implantation was > 50% lower than females infected at E4.5. These results demonstrate that pre-implantation ZIKV infection of trophectoderm leads to miscarriage or spontaneous abortion. Moreover, pre- and peri-implantation ZIKV infects trophectoderm cells that propagate virus over time causing cell death in neural progenitors. Cumulatively, these data demonstrate that vertical pre- and peri-implantation ZIKV infection of trophectoderm impairs fetal development and causes neural progenitor cell death, elucidating a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.
2019-08-16 | GSE133254 | GEO
Project description:Implantation of the early embryo—the blastocyst—in the uterine wall to establish a pregnancy is remarkably inefficient in humans for reasons that remain largely unexplained1–3. In recent years, the volume of gene expression data from human preimplantation embryos has rapidly accumulated; however, prioritization of these data to discover specific genes that determine successful implantation is significantly hindered by ethical and experimental constraints. Here, we combine clinical morphologic grading with transcriptome analysis of matched trophectoderm (TE) and inner cell mass (ICM) samples to identify specific genes and cell-cell interactions differentially activated in human blastocysts of high and low implantation potential genome-wide. This allowed us to develop the first prioritized list of genes and cell-cell interactions associated with successful implantation. Employing multiple machine learning approaches, we identified TE and ICM genes that distinguish embryos of high and low implantation potential and found that gene expression within the ICM best predicts implantation. Unexpectedly, we discovered that blastocysts of low implantation potential share defects in the formation of the extraembryonic primitive endoderm (PrE) and the PrE-associated extracellular matrix network. Our results support a model in which successful implantation is most strongly influenced by factors and signals from the ICM, and suggest that defective PrE development, in particular, is a common cause of failed implantation in humans.
2024-01-31 | GSE136106 | GEO
Project description:Selection of high-quality embryos is important to achieve successful pregnancy in assisted reproductive technology (ART). Recently, it has been debated whether RNA-sequencing (RNA-seq) should be applied to ART to predict embryo quality. However, the information on which genes can serve as markers for pregnant expectancy is limited. Furthermore, there is no information on which transcriptome of trophectoderm (TE) or inner cell mass (ICM) is more highly correlated with pregnant expectancy. Here we performed RNA-seq analysis for TE and ICM, respectively, in human blastocysts of which the expectation of pregnancy was retrospectively determined by the clinical outcomes of 1,890 cases of frozen-thawed blastocyst transfer. We identified dozens of genes that were correlated with the expected pregnancy rate in ICM and TE, respectively, with a larger number of genes identified in TE. Importantly, downregulated genes in TE of blastocysts classified as having lower expectation of pregnancy included tight junction-related genes, such as CXADR, CLDN10, and ATP1B1, which were implicated in peri-implantation development. Additionally, we showed that aneuploidy estimation by RNA-seq datasets does not correlate with pregnancy expectation. Our study thus provide an expanded list of candidate genes for prediction of pregnancy in human blastocyst embryos.
2022-09-30 | GSE205171 | 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.
2012-07-09 | GSE33025 | GEO
Project description:Our data provided a genome-wide DNA methylation landscape of human early development embryos, including human MII oocytes, sperm, zygotes, 2-cell to 8-cell embryos, morula, blastocyst and postimplantation embryos at single base resolution. In total, 44 samples including biological and technical replicates, from 12 different human embryo development stages were analyzed, including two metaphase II oocytes, two zygotes, three first polar bodies, two second polar bodies, four sperm samples, two 2-cell-stage embryos, two 4-cell-stage embryos, three 8-cell-stage embryos, three morulae, three inner cell masses (ICMs) and three trophectoderms (TEs) seperated from late blastocysts, and three post-implantation embryos. In addition, 12 different human embryo development stages were analyzed, including metaphase II oocytes, zygotes, first polar bodies, second polar bodies, sperm samples, 2-cell-stage embryos, 4-cell-stage embryos, 8-cell-stage embryos, morulae, inner cell masses (ICMs) and trophectoderms (TEs) seperated from late blastocysts, and post-implantation embryos.
2014-07-22 | E-GEOD-49828 | biostudies-arrayexpress
Project description:Implantation is a milestone event during mammalian embryogenesis. Due to the extreme difficulty of obtaining in vivo human early post-implantation embryos, the gene regulatory network and epigenetics controlling human embryo implantation remains elusive. Here, combining an in vitro culture system for human post-implantation development and single-cell omics sequencing technologies, over 10,000 single cells at five representative stages of pre/post-implantation development were systematically analyzed. Unsupervised dimensionality reduction and clustering algorithm of the transcriptome data show stepwise implantation routes for the epiblast, primitive endoderm, and trophectoderm lineages, suggesting preparation for the establishment of a mother-to-offspring connection after implantation. Female embryos showed asynchronous progress of dosage loss of X chromosomes during implantation. Furthermore, using the single cell trio-Seq (scTrio-Seq) strategy, re-methylation of the genomes of all the three lineages was unambiguously revealed. Surprisingly, the genome re-methylation of PE lineage were much slower than both EPI and TE lineages during the implantation process, indicating distinct methylome features between EPI and PE although both of which were derived from ICM. Collectively, our work paves the way for understanding the complex molecular mechanisms that regulate human embryo implantation, informing new insights and future efforts in early embryonic development and reproductive medicine.
| EGAS00001003443 | EGA