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Carlos Simon - One of the best experts on this subject based on the ideXlab platform.
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prediction model for aneuploidy in early Human Embryo development revealed by single cell analysis
Nature Communications, 2015Co-Authors: Carlos Simon, Maria Verarodriguez, Shawn L Chavez, Carmen Rubio, Renee Reijo A PeraAbstract:Aneuploidies are prevalent in the Human Embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT-qPCR to simultaneously obtain information from all cells that compose a Human Embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid Embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid Embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid Embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an Embryo is likely determined as early as the pronuclear stage and may be predicted by a 12-gene transcriptomic signature.
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Embryonic implantation and leukocyte transendothelial migration different processes with similar players
The FASEB Journal, 2005Co-Authors: Francisco Dominguez, Maria Yanezmo, Francisco Sanchezmadrid, Carlos SimonAbstract:A clear parallelism between the different steps in Human Embryo-endometrial apposition/adhesion/invasion and leukocyte-endothelium rolling/adhesion/extravasation can be established. During Human im...
Maria Verarodriguez - One of the best experts on this subject based on the ideXlab platform.
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origin and composition of cell free dna in spent medium from Human Embryo culture during preimplantation development
Human Reproduction, 2018Co-Authors: Maria Verarodriguez, Antonio Diezjuan, Jorge Jimenezalmazan, S Martinez, Roser Navarro, Amparo Mercader, Marcos Meseguer, David Blesa, Inmaculada Moreno, Diana ValbuenaAbstract:STUDY QUESTION What is the origin and composition of cell-free DNA in Human Embryo spent culture media? SUMMARY ANSWER Cell-free DNA from Human Embryo spent culture media represents a mix of maternal and Embryonic DNA, and the mixture can be more complex for mosaic Embryos. WHAT IS KNOWN ALREADY In 2016, ~300 000 Human Embryos were chromosomally and/or genetically analyzed using preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders (PGT-M) before transfer into the uterus. While progress in genetic techniques has enabled analysis of the full karyotype in a single cell with high sensitivity and specificity, these approaches still require an Embryo biopsy. Thus, non-invasive techniques are sought as an alternative. STUDY DESIGN, SIZE, DURATION This study was based on a total of 113 Human Embryos undergoing trophectoderm biopsy as part of PGT-A analysis. For each Embryo, the spent culture media used between Day 3 and Day 5 of development were collected for cell-free DNA analysis. In addition to the 113 spent culture media samples, 28 media drops without Embryo contact were cultured in parallel under the same conditions to use as controls. In total, 141 media samples were collected and divided into two groups: one for direct DNA quantification (53 spent culture media and 17 controls), the other for whole-genome amplification (60 spent culture media and 11 controls) and subsequent quantification. Some samples with amplified DNA (N = 56) were used for aneuploidy testing by next-generation sequencing; of those, 35 samples underwent single-nucleotide polymorphism (SNP) sequencing to detect maternal contamination. Finally, from the 35 spent culture media analyzed by SNP sequencing, 12 whole blastocysts were analyzed by fluorescence in situ hybridization (FISH) to determine the level of mosaicism in each Embryo, as a possible origin for discordance between sample types. PARTICIPANTS/MATERIALS, SETTING, METHODS Trophectoderm biopsies and culture media samples (20 μl) underwent whole-genome amplification, then libraries were generated and sequenced for an aneuploidy study. For SNP sequencing, triads including trophectoderm DNA, cell-free DNA, and follicular fluid DNA were analyzed. In total, 124 SNPs were included with 90 SNPs distributed among all autosomes and 34 SNPs located on chromosome Y. Finally, 12 whole blastocysts were fixed and individual cells were analyzed by FISH using telomeric/centromeric probes for the affected chromosomes. MAIN RESULTS AND THE ROLE OF CHANCE We found a higher quantity of cell-free DNA in spent culture media co-cultured with Embryos versus control media samples (P ≤ 0.001). The presence of cell-free DNA in the spent culture media enabled a chromosomal diagnosis, although results differed from those of trophectoderm biopsy analysis in most cases (67%). Discordant results were mainly attributable to a high percentage of maternal DNA in the spent culture media, with a median percentage of Embryonic DNA estimated at 8%. Finally, from the discordant cases, 91.7% of whole blastocysts analyzed by FISH were mosaic and 75% of the analyzed chromosomes were concordant with the trophectoderm DNA diagnosis instead of the cell-free DNA result. LIMITATIONS, REASONS FOR CAUTION This study was limited by the sample size and the number of cells analyzed by FISH. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to combine chromosomal analysis of cell-free DNA, SNP sequencing to identify maternal contamination, and whole-blastocyst analysis for detecting mosaicism. Our results provide a better understanding of the origin of cell-free DNA in spent culture media, offering an important step toward developing future non-invasive karyotyping that must rely on the specific identification of DNA released from Human Embryos. STUDY FUNDING/ COMPETING INTEREST This work was funded by Igenomix S.L. There are no competing interests.
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prediction model for aneuploidy in early Human Embryo development revealed by single cell analysis
Nature Communications, 2015Co-Authors: Carlos Simon, Maria Verarodriguez, Shawn L Chavez, Carmen Rubio, Renee Reijo A PeraAbstract:Aneuploidies are prevalent in the Human Embryo and impair proper development, leading to cell cycle arrest. Recent advances in imaging and molecular and genetic analyses are postulated as promising strategies to unveil the mechanisms involved in aneuploidy generation. Here we combine time-lapse, complete chromosomal assessment and single-cell RT-qPCR to simultaneously obtain information from all cells that compose a Human Embryo until the approximately eight-cell stage (n=85). Our data indicate that the chromosomal status of aneuploid Embryos (n=26), including those that are mosaic (n=3), correlates with significant differences in the duration of the first mitotic phase when compared with euploid Embryos (n=28). Moreover, gene expression profiling suggests that a subset of genes is differentially expressed in aneuploid Embryos during the first 30 h of development. Thus, we propose that the chromosomal fate of an Embryo is likely determined as early as the pronuclear stage and may be predicted by a 12-gene transcriptomic signature.
Shahbazi, Marta N - One of the best experts on this subject based on the ideXlab platform.
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A single cell characterisation of Human Embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Molè, Matteo A, Coorens, Tim H H, Shahbazi, Marta N, Weberling Antonia, Weatherbee, Bailey A T, Gantner, Carlos W, Sancho-serra Carmen, Richardson Lucy, Drinkwater Abbie, Syed NajmaAbstract:Following implantation, the Human Embryo undergoes major morphogenetic transformations that establish the future body plan. While the molecular events underpinning this process are established in mice, they remain unknown in Humans. Here we characterise key events of Human Embryo morphogenesis, in the period between implantation and gastrulation, using single-cell analyses and functional studies. First, the Embryonic epiblast cells transition through different pluripotent states and act as a source of FGF signals that ensure proliferation of both Embryonic and extra-Embryonic tissues. In a subset of Embryos, we identify a group of asymmetrically positioned extra-Embryonic hypoblast cells expressing inhibitors of BMP, NODAL and WNT signalling pathways. We suggest that this group of cells can act as the anterior singalling centre to pattern the epiblast. These results provide insights into pluripotency state transitions, the role of FGF signalling and the specification of anterior-posterior axis during Human Embryo development
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A single cell characterisation of Human Embryogenesis identifies pluripotency transitions and putative anterior hypoblast centre.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Molè, Matteo A, Tim H. H. Coorens, Shahbazi, Marta N, Weberling Antonia, Sancho-serra Carmen, Richardson Lucy, Drinkwater Abbie, Weatherbee Bailey, Gantner Carlos, Syed NajmaAbstract:Following implantation, the Human Embryo undergoes major morphogenetic transformations that establish the future body plan. While the molecular events underpinning this process are established in mice, they remain unknown in Humans. Here we characterise key events of Human Embryo morphogenesis, in the period between implantation and gastrulation, using single-cell analyses and functional studies. First, the Embryonic epiblast cells transition through different pluripotent states and act as a source of FGF signals that ensure proliferation of both Embryonic and extra-Embryonic tissues. In a subset of Embryos, we identify a group of asymmetrically positioned extra-Embryonic hypoblast cells expressing inhibitors of BMP, NODAL and WNT signalling pathways. We suggest that this group of cells can act as the anterior singalling centre to pattern the epiblast. These results provide insights into pluripotency state transitions, the role of FGF signalling and the specification of anterior-posterior axis during Human Embryo development.M.N.S is funded by the European Molecular Biology Organisation (EMBO, Advanced EMBO fellowship) and UKRI Medical Research Council (MC_UP_1201/24). B.A.T.W is funded by the Gates Cambridge Trust. Work in the laboratory of M.Z-G. is supported by grants from the Wellcome Trust (207415/Z/17/Z), Open Philanthropy/Silicon Valley, Curci and Weston Havens Foundations. S.B is funded by the Wellcome Trust (Sanger core funding and personal fellowship to S.B.)
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An in vitro stem cell model of Human epiblast and yolk sac interaction.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Kirsty Ml Mackinlay, Bailey A. T. Weatherbee, Souza Rosa Viviane, Handford, Charlotte E, Hudson George, Coorens Tim, Pereira Lygia, Behjati Sam, Vallier Ludovic, Shahbazi, Marta NAbstract:Human Embryogenesis entails complex signalling interactions between Embryonic and extra-Embryonic cells. However, how extra-Embryonic cells direct morphogenesis within the Human Embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate Human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation Human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in Human Embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse Embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the Human Embryo and propose YSLCs as a tool for studying post-implantation Human Embryo development in vitro.
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An in vitro stem cell model of Human epiblast and yolk sac interaction
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Kirsty Ml Mackinlay, Bailey A. T. Weatherbee, Souza Rosa Viviane, Handford, Charlotte E, Hudson George, Coorens Tim, Pereira Lygia, Behjati Sam, Vallier Ludovic, Shahbazi, Marta NAbstract:Funder: European Molecular Biology Laboratory; FundRef: http://dx.doi.org/10.13039/100013060Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735Funder: Gates Cambridge Trust; FundRef: http://dx.doi.org/10.13039/501100005370Funder: European Molecular Biology Organization; FundRef: http://dx.doi.org/10.13039/100004410Human Embryogenesis entails complex signalling interactions between Embryonic and extra-Embryonic cells. However, how extra-Embryonic cells direct morphogenesis within the Human Embryo remains largely unknown due to a lack of relevant stem cell models. Here, we have established conditions to differentiate Human pluripotent stem cells (hPSCs) into yolk sac-like cells (YSLCs) that resemble the post-implantation Human hypoblast molecularly and functionally. YSLCs induce the expression of pluripotency and anterior ectoderm markers in Human Embryonic stem cells (hESCs) at the expense of mesoderm and endoderm markers. This activity is mediated by the release of BMP and WNT signalling pathway inhibitors, and, therefore, resembles the functioning of the anterior visceral endoderm signalling centre of the mouse Embryo, which establishes the anterior-posterior axis. Our results implicate the yolk sac in epiblast cell fate specification in the Human Embryo and propose YSLCs as a tool for studying post-implantation Human Embryo development in vitro
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Mechanism of cell polarisation and first lineage segregation in the Human Embryo
2020Co-Authors: Zhu Meng, Molè, Matteo A, Shahbazi, Marta N, Martin Angel, Zhang Chuanxin, Sozen Berna, Borsos Mate, Mandelbaum, Rachel S., Paulson, Richard J., Esbert MargaAbstract:The formation of differential cell lineages in the mammalian blastocyst from the totipotent zygote is crucial for implantation and the success of the whole pregnancy. The first lineage segregation generates the polarised trophectoderm (TE) tissue, which forms the placenta, and the apolar inner cell mass (ICM), which mainly gives rise to all foetal tissues and also the yolk sac. The mechanism underlying this cell fate segregation has been extensively studied in the mouse Embryo. However, when and how it takes place in the Human Embryo remains unclear. Here, using time-lapse imaging and 325 surplus Human Embryos, we provide a detailed characterisation of morphological events and transcription factor expression and localisation to understand how they lead to the first lineage segregation in Human Embryogenesis. We show that the first lineage segregation of the Human Embryo is triggered by cell polarisation that occurs at the 8-cell stage in two sequential steps. In the first step, F-actin becomes apically polarised concomitantly with Embryo compaction. In the second step, the Par complex becomes polarised to form the apical cellular domain. Mechanistically, we show that activation of Phospholipase C (PLC) triggers actin polarisation and is therefore essential for apical domain formation, as is the case in mouse Embryos. Finally, we show that, in contrast to the mouse Embryo, the key extra-Embryonic determinant GATA3 is expressed not only in extra-Embryonic lineage precursors upon blastocyst formation. However, the cell polarity machinery enhances the expression and nuclear accumulation of GATA3. In summary, our results demonstrate for the first time that cell polarisation reinforces the first lineage segregation in the Human Embryo
Susana Lopes - One of the best experts on this subject based on the ideXlab platform.
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Characterization of migratory primordial germ cells in the aorta-gonad-mesonephros of a 4.5-week-old Human Embryo: a toolbox to evaluate in vitro early gametogenesis
Molecular human reproduction, 2018Co-Authors: Maria Gomes Fernandes, Daniela Cf Salvatori, Monika Bialecka, Susana LopesAbstract:Study question Which set of antibodies can be used to identify migratory and early post-migratory Human primordial germ cells (hPGCs)? Study finding We validated the specificity of 33 antibodies for 31 markers, including POU5F1, NANOG, PRDM1 and TFAP2C as specific markers of hPGCs at 4.5 weeks of development of Carnegie stage (CS12-13), whereas KIT and SOX17 also marked the intra-aortic hematopoietic stem cell cluster in the aorta-gonad-mesonephros (AGM). What is known already The dynamics of gene expression during germ cell development in mice is well characterized and this knowledge has proved crucial to allow the development of protocols for the in vitro derivation of functional gametes. Although there is a great interest in generating Human gametes in vitro, it is still unclear which markers are expressed during the early stages of hPGC development and many studies use markers described in mouse to benchmark differentiation of Human PGC-like cells (hPGCLCs). Early post-implantation development differs significantly between mice and Humans, and so some germ cells markers, including SOX2, SOX17, IFITM3 and ITGA6 may not identify mPGCs and hPGCs equally well. Study design, size, duration This immunofluorescence study investigated the expression of putative hPGC markers in the caudal part of a single Human Embryo at 4.5 weeks of development. Participants/materials, setting, methods We have investigated by immunofluorescence the expression of a set of 33 antibodies for 31 markers, including pluripotency, germ cell, adhesion, migration, surface, mesenchymal and epigenetic markers on paraffin sections of the caudal part, including the AGM region, of a single Human Embryo (CS12-13). The Human material used was anonymously donated with informed consent from elective abortions without medical indication. Main results and the role of chance We observed germ cell specific expression of NANOG, TFAP2C and PRDM1 in POU5F1+ hPGCs in the AGM. The epigenetic markers H3K27me3 and 5mC were sufficient to distinguish hPGCs from the surrounding somatic cells. Some mPGC-markers were not detected in hPGCs, but marked other tissues; whereas other markers, such as ALPL, SOX17, KIT, TUBB3, ITGA6 marked both POU5F1+ hPGCs and other cells in the AGM. We used a combination of multiple markers, immunostaining different cellular compartments when feasible, to decrease the chance of misidentifying hPGCs. Large scale data Non-applicable. Limitations reasons for caution Material to study early Human development is unique and very rare thus restricting the sample size. We have used a combination of antibodies limited by the number of paraffin sections available. Wider implications of the findings Most of our knowledge on early gametogenesis has been obtained from model organisms such as mice and is extrapolated to Humans. However, since there is a dedicated effort to produce Human artificial gametes in vitro, it is of great importance to determine the expression and specificity of Human-specific germ cell markers. We provide a systematic analysis of the expression of 31 different markers in paraffin sections of a CS12-13 Embryo. Our results will help to set up a toolbox of markers to evaluate protocols to induce hPGCLCs in vitro. Study funding and competing interest(s) M.G.F. was funded by Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BD/78689/2011] and S.M.C.S.L. was funded by the Interuniversity Attraction Poles (IAP, P7/07) and the European Research Council Consolidator (ERC-CoG-725722-OVOGROWTH). The authors declare no conflict of interest.
Esbert Marga - One of the best experts on this subject based on the ideXlab platform.
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Human Embryo polarization requires PLC signaling to mediate trophectoderm specification
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Zhu Meng, Molè, Matteo A, Martin Angel, Zhang Chuanxin, Sozen Berna, Borsos Mate, Mandelbaum, Rachel S., Paulson, Richard J., Shahbazi Marta, Esbert MargaAbstract:Funder: Open Philanthropy Project; FundRef: http://dx.doi.org/10.13039/100014895Funder: Curci and Weston Heavens FoundationsFunder: European molecular biology organisation; FundRef: http://dx.doi.org/10.13039/100004410Apico-basal polarization of cells within the Embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the Human Embryo and its timing during Embryogenesis have remained unknown. Here, we show that Human Embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8–16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of Embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in Human Embryos
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Human Embryo polarization requires PLC signaling to mediate trophectoderm specification.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Zhu Meng, Molè, Matteo A, Martin Angel, Zhang Chuanxin, Sozen Berna, Borsos Mate, Mandelbaum, Rachel S., Paulson, Richard J., Shahbazi Marta, Esbert MargaAbstract:Funder: Open Philanthropy ProjectFunder: Curci and Weston Heavens FoundationsFunder: European molecular biology organisationApico-basal polarization of cells within the Embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the Human Embryo and its timing during Embryogenesis have remained unknown. Here, we show that Human Embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8-16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of Embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in Human Embryos
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Human Embryo polarization requires PLC signaling to mediate trophectoderm specification.
'Organisation for Economic Co-Operation and Development (OECD)', 2021Co-Authors: Zhu Meng, Molè, Matteo A, Martin Angel, Zhang Chuanxin, Sozen Berna, Borsos Mate, Mandelbaum, Rachel S., Paulson, Richard J., Shahbazi Marta, Esbert MargaAbstract:Apico-basal polarization of cells within the Embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the Human Embryo and its timing during Embryogenesis have remained unknown. Here, we show that Human Embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8-16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of Embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in Human Embryos.Wellcome Trust (WT): Magdalena Zernicka-Goetz, 207415/Z/17/Z; Open Philanthropy Project: Magdalena Zernicka-Goetz; Curci and Weston Heavens Foundations: Magdalena Zernicka-Goetz; Leverhulme Trust: Meng Zhu, RPG-2018-085; European molecular biology organisation: Marta Shahbazi; UKRI | Medical Research Council (MRC): Marta Shahbazi, MC_UP_1201/24; MOST | National Key Research and Development Program of China (973 Program): Zijiang Chen, 2018YFC1004000; Shandong Provincial Key Research and Development Program: Zijiang Chen, 2018YFJH0504 The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication
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Mechanism of cell polarisation and first lineage segregation in the Human Embryo
2020Co-Authors: Zhu Meng, Molè, Matteo A, Shahbazi, Marta N, Martin Angel, Zhang Chuanxin, Sozen Berna, Borsos Mate, Mandelbaum, Rachel S., Paulson, Richard J., Esbert MargaAbstract:The formation of differential cell lineages in the mammalian blastocyst from the totipotent zygote is crucial for implantation and the success of the whole pregnancy. The first lineage segregation generates the polarised trophectoderm (TE) tissue, which forms the placenta, and the apolar inner cell mass (ICM), which mainly gives rise to all foetal tissues and also the yolk sac. The mechanism underlying this cell fate segregation has been extensively studied in the mouse Embryo. However, when and how it takes place in the Human Embryo remains unclear. Here, using time-lapse imaging and 325 surplus Human Embryos, we provide a detailed characterisation of morphological events and transcription factor expression and localisation to understand how they lead to the first lineage segregation in Human Embryogenesis. We show that the first lineage segregation of the Human Embryo is triggered by cell polarisation that occurs at the 8-cell stage in two sequential steps. In the first step, F-actin becomes apically polarised concomitantly with Embryo compaction. In the second step, the Par complex becomes polarised to form the apical cellular domain. Mechanistically, we show that activation of Phospholipase C (PLC) triggers actin polarisation and is therefore essential for apical domain formation, as is the case in mouse Embryos. Finally, we show that, in contrast to the mouse Embryo, the key extra-Embryonic determinant GATA3 is expressed not only in extra-Embryonic lineage precursors upon blastocyst formation. However, the cell polarity machinery enhances the expression and nuclear accumulation of GATA3. In summary, our results demonstrate for the first time that cell polarisation reinforces the first lineage segregation in the Human Embryo