0000000000041508

AUTHOR

Susan J. Fisher

showing 4 related works from this author

Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.

2016

Pre-eclampsia (PE), which affects ∼8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes. The results showed a significant expansion of the CTB layer. The cells displayed enhanced expression of stage-specific antigens that extravillous CTBs normally upregulate as they exit the placenta. Transcriptomics revealed the dysregulated expression of many genes (e.g. placental proteins, markers of oxidative stress). We confirmed an sPE-related incr…

0301 basic medicineAdultSpiral arteryTranscription GeneticPlacentaHuman DevelopmentCTBSExtraembryonic MembranesBiology210Andrology03 medical and health sciences0302 clinical medicineDownregulation and upregulationPre-EclampsiaPregnancyPlacentamedicineHumansPregnancy-Associated Plasma Protein-AMolecular BiologyCytotrophoblastPAPPA1Cell ProliferationFetus030219 obstetrics & reproductive medicineCytotrophoblastPlacentationGene Expression Regulation DevelopmentalPreterm birthChorionPlacentationTrophoblastsOxidative Stress030104 developmental biologymedicine.anatomical_structureImmunologyembryonic structuresKeratinsFemaleCytotrophoblastsTranscriptomeDevelopmental BiologyProtein BindingHumanDevelopment (Cambridge, England)
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Disruption of apical-basal polarity of human embryonic stem cells enhances hematoendothelial differentiation

2007

Abstract During murine development, the formation of tight junctions and acquisition of polarity are associated with allocation of the blastomeres on the outer surface of the embryo to the trophoblast lineage, whereas the absence of polarization directs cells to the inner cell mass. Here, we report the results of ultrastructural analyses that suggest a similar link between polarization and cell fate in human embryos. In contrast, the five human embryonic stem cell (hESC) lines displayed apical-basal, epithelial-type polarity with electron-dense tight junctions, apical microvilli, and asymmetric distribution of organelles. Consistent with these findings, molecules that are components of tigh…

Embryoid bodyBiologyCell fate determinationMiceCell polarityAnimalsHumansInner cell massCells CulturedEmbryonic Stem Cellsreproductive and urinary physiologyembryoid body formationTight junctionMesenchymal stem cellapical-basal polarityCell PolarityCell DifferentiationEpithelial CellsCell Biologyinner cell masshuman embryonic stem cellsEmbryonic stem cellHematopoiesisCell biologyDrug CombinationsIntercellular JunctionsPhenotypeembryonic structuresMolecular Medicinehernatoendothelial differentiationProteoglycansCollagenEndothelium VascularLamininStem cellDevelopmental Biology
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Human stem cells from single blastomeres reveal pathways of embryonic or trophoblast fate specification.

2015

Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines (designated UCSFB1-10) from single blastomeres of four 8-cell embryos and one 12-cell embryo from a single couple. Compared with numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation patterns that were, in part, indicative of trophoblast competence. At a transcriptional level, UCSFB lines from different embryos were often more closely related than those from the same embryo. As predicted by the transcriptomic data, immunolocalization of EOMES, T brachyury, GDF15 and active β-catenin reve…

BlastomeresTranscription GeneticCellular differentiationMedical and Health SciencesEmbryo Culture TechniquesEpigenomeNeural Stem CellsDevelopmentalMyocytes Cardiacbeta CateninOligonucleotide Array Sequence AnalysisEndodermGene Expression Regulation DevelopmentalEmbryoCell DifferentiationBiological SciencesStem Cells and RegenerationTrophoblastsmedicine.anatomical_structureembryonic structuresStem Cell Research - Nonembryonic - Non-HumanStem cellEndodermCardiacTranscriptionBrachyuryGrowth Differentiation Factor 151.1 Normal biological development and functioningBiologyCell LineGeneticUnderpinning researchmedicineGeneticsHumansHuman embryoCell LineageBlastocystMolecular BiologyEmbryonic Stem CellsMyocytesBlastomereHuman embryonic stem cellGene Expression ProfilingTrophoblastFibroblastsDNA MethylationStem Cell ResearchHuman trophoblast stem cellEmbryonic stem cellMolecular biology102Fate specificationBlastocystGene Expression RegulationGeneric health relevanceTranscriptomeDevelopmental Biology
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Transcriptomic Signature of Trophoblast Differentiation in a Human Embryonic Stem Cell Model1

2011

Identification of genes involved in trophoblast differentiation is of great interest in understanding cellular and molecular mechanisms involved in placental development and is relevant clinically to fetal development, fertility, and maternal health. Herein, we investigated differentiation of human embryonic stem cells (hESCs) down the trophoblast lineage by culture with bone morphogenetic protein 4 (BMP4) over a 10-day period. Within 2 days, the stemness markers POU5F1 and NANOG were markedly down-regulated, followed temporally by up-regulation of the CDX2, KRT7, HLA-G, ID2, CGA, and CGB trophoblast markers. To understand, on a global scale, changes in the transcriptome during the differen…

GeneticsHomeobox protein NANOGCellular differentiationWnt signaling pathwayTrophoblastCell BiologyGeneral MedicineBiologyCell biologyGene expression profilingTranscriptomemedicine.anatomical_structureReproductive Medicineembryonic structuresmedicineStem cellDevelopmental biologyreproductive and urinary physiologyBiology of Reproduction
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