PRMT1 recruitment and H3R4Me32a modfification in control and PRMT1-depleted trophoblast progenitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE295846 | GEO | 2026/06/15
REPOSITORIES: GEO
Dataset's files
Items per page: 5 1 - 5 of 11 |
Similar Datasets
Project description:The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout (KO) screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.
2023-11-09 | GSE244253 | GEO
Project description:The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout (KO) screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.
2023-11-09 | GSE244252 | GEO
Project description:The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout (KO) screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.
2023-11-09 | GSE244254 | GEO
Project description:Zika virus (ZIKV) infection during pregnancy results in an increased risk of spontaneous abortion and vertical transmission across placenta results in severe congenital defects in newborns. While the infectivity and pathological effects of ZIKV on the placental trophoblast progenitor cells in early human embryos remains largely unknown. Here, using the human trophoblast stem cells (hTSCs) isolated from human blastocyst, we showed that hTSCs were permissive to ZIKV infection, while resistance to ZIKV increased with differentiation. Combined CRISPR/Cas9-mediated gene knockout and RNA-seq assays, we demonstrated that the intrinsic expression of AXL and TIM-1, as well as the absence of potent interferon (IFN)-stimulated genes (ISGs), contributed to the high sensitivity of hTSCs to ZIKV. Furthermore, using our newly developed hTSC-derived 3 dimensional (3D) placental trophoblast organoid model, we demonstrated that ZIKV infection completely disrupted the structure of mature hTSC-organoids and inhibited syncytialization. Overall, our results clearly demonstrated that hTSCs represented the major target cells of ZIKV, and a possible reduced syncytialization may result from ZIKV infection of early developing placenta. These findings deepened our understanding of the characteristics and consequences of ZIKV infection of trophoblast stem cells in early human embryo.
2023-08-03 | GSE229702 | GEO
Project description:The recent derivation of bona fide human trophoblast stem cells (hTSCs) significantly improved our ability to study human placental biology and pathologies, but few studies have investigated the molecular regulators of hTSC identity. Therefore, we utilized a genome-wide CRISPR-Cas9 knockout screen to comprehensively define genes essential for or restricting the fitness of hTSCs. The resulting essential and growth-restricting genes include both well-established and potentially novel trophoblast regulators. We referenced our data to those of similar genetic screens performed in cancer cell lines and primed human pluripotent stem cells (hPSCs), as well as gene expression data of the early human embryos, to identify potential hTSC-specific and -enriched regulators. Among those are TEAD1, a gene previously reported to be dispensable for mouse placentation6. However, in the human trophoblast context, TEAD1 targets many hTSC regulators and plays a major role in its specification and maintenance. Overall, our study presents the first CRISPR/Cas9 knockout screen in a human extraembryonic lineage and provides a valuable resource for future trophoblast research.
2022-04-11 | GSE172329 | GEO
Project description:Wnt signaling are essential for the maintenance and differentiation of stem/progenitor cells, including trophoblast stem cells during placental development. Hyper-activation of Wnt signaling has been shown to relate with human trophoblast diseases. However, litter is known about the impact and underlying mechanisms of excessive Wnt signaling during placental trophoblast development. In the present work, we found that Sfrp1,5 double mutant mouse exhibited disturbed trophoblast differentiation in the placental ectoplacental cone (EPC), where the precursors of secondary trophoblast giant cells (TGCs) and trophoblast cells in the spongiotrophoblast layer are located. Employing mouse models expressing a trunked β-catenin with exon 3 deletion globally and trophoblast-specifically, combining cultured trophoblast stem cells, we found that hyper-activation of canonical Wnt pathway exhausted the trophoblast precursor cells in the EPC, resulting in the overabundance of giant cells at the expense of spongiotrophoblast cells. Further examination uncovered that hyper-activation of canonical Wnt pathway disturbed trophoblast differentiation in the EPC via repressing Mash2 expression. Collectively, our findings demonstrate that appropriate canonical Wnt-β-catenin pathway is essential for EPC trophoblast differentiation during placental development. Our work also has high clinical relevance, since abnormal Wnt signaling are often associated with trophoblast-related diseases.
2020-03-06 | GSE146433 | GEO
Project description:Wnt signaling are essential for the maintenance and differentiation of stem/progenitor cells, including trophoblast stem cells during placental development. Hyper-activation of Wnt signaling has been shown to relate with human trophoblast diseases. However, litter is known about the impact and underlying mechanisms of excessive Wnt signaling during placental trophoblast development. In the present work, we found that Sfrp1,5 double mutant mouse exhibited disturbed trophoblast differentiation in the placental ectoplacental cone (EPC), where the precursors of secondary trophoblast giant cells (TGCs) and trophoblast cells in the spongiotrophoblast layer are located. Employing mouse models expressing a trunked β-catenin with exon 3 deletion globally and trophoblast-specifically, combining cultured trophoblast stem cells, we found that hyper-activation of canonical Wnt pathway exhausted the trophoblast precursor cells in the EPC, resulting in the overabundance of giant cells at the expense of spongiotrophoblast cells. Further examination uncovered that hyper-activation of canonical Wnt pathway disturbed trophoblast differentiation in the EPC via repressing Mash2 expression. Collectively, our findings demonstrate that appropriate canonical Wnt-β-catenin pathway is essential for EPC trophoblast differentiation during placental development. Our work also has high clinical relevance, since abnormal Wnt signaling are often associated with trophoblast-related diseases.
2020-03-06 | GSE146432 | GEO
Project description:To investigate the role of ISRIB in human trophoblast stem cell(hTSC) maintenance without activation of WNT & TGFβ. We performed gene expression profiling analysis using data obtained from RNA-seq of hTSCs cultured in the medium contained 0.5 µM ISRIB and 10 µM Y27652, after removing CHIR99021, A83-01, SB431542.
2023-12-31 | GSE221409 | GEO
Project description:Transcriptional deregulation plays a major role in acute myeloid leukemia, identification of epigenetic modifying enzymes essential for the maintenance of oncogenic transcription programs holds the key to better understanding the biology and designing effective therapeutic strategies for the disease. Here we provide experimental evidence showing the functional involvement and therapeutic potentials of targeting PRMT1 with H4R3 methyltransferase activity in various MLL and non-MLL leukemias. PRMT1 is necessary but not sufficient for leukemic transformation, which requires co-recruitment of KDM4C with H3K9 demethylase activity by chimeric transcription factors to mediate epigenetic reprogramming. Inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions and MOZ-TIF2, revealing a novel and targetable epigenetic circuitry mediated by PRMT1 and KDM4C in acute leukemia.
2016-01-14 | E-MTAB-3322 | biostudies-arrayexpress
Project description:The placental DNA methylation landscape is unique, with widespread partially methylated domains (PMDs) and hundreds of placental-specific imprinted domains. Furthermore, the placental ‘methylome’ has been the focus of extensive study for links with pregnancy complications. Human trophoblast stem cells (hTSCs) offer exciting potential for functional epigenetic studies; however, whether the hTSC epigenome recapitulates primary cytotrophoblast, remains poorly described. In this study, we demonstrate that hTSCs exhibit an atypical methylome, with DNA methylation present over transcribed gene bodies but a complete loss of placental PMDs. Using single-cell RNA-seq from human embryogenesis, hTSCs display a notable absence of DNMT3L expression. Ectopic expression of DNMT3L in hTSCs restored placental PMDs. DNMT3L-expressing hTSCs showed comparable stemness but failed to syncytialise in organoid culture, associated with hypermethylation of STB transcription factor motifs. These findings reveal that DNMT3L is essential in establishing the human placental methylome and that DNMT3L downregulation is necessary for successful trophoblast differentiation.
2025-01-08 | GSE266195 | GEO