Next generation trophoblast organoids with apical-out trophoblast polarity and central villous core-like cavity
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PROVIDER: PRJNA1137241 | ENA |
REPOSITORIES: ENA
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Project description:Human trophoblast organoid serves as a revolutionary tool for studying trophoblast cell development and maternal-fetal interactions. However, currently reported trophoblast organoids exhibited opposite trophoblast polarity to in vivo or a solid cell spheroid lacking of central villous core-like cavity, both of which fail to model the physiological structure of in vivo placenta villi. Here, using human naïve embryonic stem cells, we constructed a trophoblast organoid with both peripheral apical-out bilaminar trophoblast cells and central villous core-like cavity, named ppTO. Besides, ppTO simulated the typical molecular and secretory features of in vivo trophoblast. Single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the development of ppTO simulated in vivo trophoblast syncytialization process and pan-trophoblast transcriptome features. Using ppTO, we revealed that the syncytialization process relied on a suppressed HIPPO signaling for initiating syncytialization and followed by a reactivated HIPPO signaling for STB maturation. By comparative study with reported organoids, we revealed the important role of the expression and orientation of polarity molecule aPKC in the formation and spatial patterning of STB within trophoblast organoids. In summary, we develop a trophoblast organoid simulating the physiological structure and molecular features of placental villous trophoblast for studying the mechanisms underlying trophoblast development and function.
2025-07-09 | GSE272513 | GEO
Project description:A central question in cell and developmental biology is how extracellular cues control the differentiation of multipotent progenitors in a dynamically changing niche. Here, we identify apical-basal polarity as the main regulator of the differentiation of multipotent pancreatic Neurogenin3+ endocrine progenitors (EPs) into the beta or alpha cell fates. We show that human EPs dynamically change their apical-basal polarity status. Whereas polarized EPs are predisposed to differentiate into beta cells rather than alpha cells, inhibiting apical-basal polarity selectively suppresses beta cell differentiation. Single-cell RNA sequencing and complementary mechanistic data demonstrate that apical-basal polarity in human EPs promotes beta cell specification via cyclic AMP (cAMP)/PKA-cAMP response element binding protein (CREB)-EGR1-mediated inhibition of ARX expression, while reduced cAMP levels in non-polarized human EPs maintain expression of ARX, leading to alpha cell differentiation. These findings identify the apical-basal polarity status of multipotent EPs as a critical epithelial feature that determines their fate into the alpha or beta cell lineages.
2025-01-01 | GSE224286 | GEO
Project description:Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis, except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription. Apically polarized (Control) and two different populations of non-polarized human mammary epithelial cells (18-alpha-glycyrrhetinic acid =AGA, and 5-aza-2'-deoxycytidine =Aza) were used for microarray analysis containing four biological replicates (1-4) for each treatment. The two treatments that cause loss of apical polarity were compared to reference apically polarized control samples using two different statistical analysis methods (FDR and HolmM-bM-^@M-^Ys).
2012-02-29 | E-GEOD-35165 | biostudies-arrayexpress
Project description:Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis, except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription.
2012-02-29 | GSE35165 | GEO
Project description:The epiblast is the first cell type that forms apical-basal polarity de novo as the mouse embryo implants into the maternal uterus, while the extraembryonic neighbours of the epiblast - trophectoderm and primitive endoderm - retain their pre-established polarity beyond implantation [1]; however, it is still unclear how the epiblast establishes apical-basal polarity de novo. Here, we focused on Rap1 signaling pathway, which is activated during the transition of the epiblast from the naïve to primed state of pluripotency during implantation [2]. Through the preestablished in vitro three-dimensional culture system [3], genetic knockouts and proximity-biotinylation analyses, we found that Rap1 integrates multiple signals that contribute to de novo formation of apical-basal polarity. Importantly, formation of apical-basal polarity in the epiblast is essential for its correct patterning and proper communication with the extraembryonic lineages. Altogether, these results not only dissect molecular details of de novo apical-basal polarity formation, but also have broader implications for epithelial polarity and development.
2022-06-14 | PXD028315 | Pride
Project description:Invasion of cytotrophoblasts into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion, mRNA signatures of purified villous (CTB, poor invasiveness) and extravillous (EVT, high invasiveness) trophoblasts isolated from first trimester human placentae and villous explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration related transcripts. Several genes involved in physiological and pathologic cell invasion, including ADAM-12,-19,-28 as well as Spondin-2, were upregulated in EVT. Pathway prediction analyses identified several functional modules associated with either the invasive or the non-invasive trophoblast phenotype. One of the genes which were downregulated in the invasive mRNA pool, heme oxygenase-1 (HO-1), was selected for functional analyses. Real-time PCR analyses, Western blottting, and immunofluorescene of first trimester placentae and differentiating villous explant cultures demonstrated downregulation of HO-1 in invasive EVT as compared to CTB. Modulation of HO-1 expression in loss-of as well as gain-of function cell models (BeWo and HTR8/SVneo, respectively) demonstrated an inverse relationship of HO-1 expression with trophoblast migration in transwell and wound healing assays. Importantly, HO-1 expression led to an increase in protein levels and activity of the nuclear hormone receptor PPARgamma. Pharmacological inhibition of PPARgamma abrogated the inhibitory effects of HO-1 on trophoblast migration. Collectively, our results demonstrate that gene expression profiling of EVT and CTB can be used to unravel novel regulators of cell invasion. Accordingly, we identify heme oxygenase-1 as a negative regulator of trophoblast motility acting via upregulation of PPARgamma. Experiment Overall Design: To identify genes potentially regulating cell invasion trophoblast cells of early human gestation with distinct invasive properties were profiled. Experiment Overall Design: Distinct gene expression signatures of highly invasive EVT (n = 6) and poorly invasive CTB (n = 5) of different first trimester placentae using Affymetrix U133A GeneChips interrogating >20,000 genes were determined.
2009-01-30 | E-GEOD-9773 | biostudies-arrayexpress
Project description:Transcriptional profiling comparison of human primary villous trophoblast and extra-villous trophoblast (VT and EVT respectively) cells, isolated from the placenta at 8 to 12 weeks gestation, with complimentary transcriptional profiling of choriocarcinoma cell lines JEG-3 and JAR. Based on phenotypic markers, JEG is frequently used as a model for EVT and JAR is used as a model for VT.
2011-04-28 | E-MTAB-429 | biostudies-arrayexpress
Project description:Placenta-specific genes and their regulation during villous trophoblast differentiation.
| PRJNA535523 | ENA
Project description:Apical-basal polarity drives pancreatic alpha/beta cell fate allocation
| PRJNA930460 | ENA
Project description:Analysis of genome-wide gene expression during the differentiation of villous trophoblasts isolated from healthy term placentas.
2019-11-25 | GSE130339 | GEO