ChIP-seq in human trophoblast stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE306709 | GEO | 2025/09/02
REPOSITORIES: GEO
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Project description:The human placenta plays vital roles in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, however, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here, we conducted integrated snRNA-seq and snATAC-seq on human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their presence in human trophoblast stem cells (hTSCs)-derived STB. Furthermore, we identified transcription factor (TF) motifs that are biased towards diverse STB nuclear lineages through their associated gene regulatory networks. The role of these TFs in STB differentiation were confirmed in the hTSCs- and trophoblast organoid-derived STB. Together, our data provide valuable insights into the heterogeneity of human STB and represents a valuable resource for interpreting its associated pregnancy complications.
2023-11-09 | GSE247037 | GEO
Project description:The human placenta plays vital roles in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, however, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here, we conducted integrated snRNA-seq and snATAC-seq on human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their presence in human trophoblast stem cells (hTSCs)-derived STB. Furthermore, we identified transcription factor (TF) motifs that are biased towards diverse STB nuclear lineages through their associated gene regulatory networks. The role of these TFs in STB differentiation were confirmed in the hTSCs- and trophoblast organoid-derived STB. Together, our data provide valuable insights into the heterogeneity of human STB and represents a valuable resource for interpreting its associated pregnancy complications.
2023-11-09 | GSE247035 | GEO
Project description:The human placenta plays vital roles in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, however, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here, we conducted integrated snRNA-seq and snATAC-seq on human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their presence in human trophoblast stem cells (hTSCs)-derived STB. Furthermore, we identified transcription factor (TF) motifs that are biased towards diverse STB nuclear lineages through their associated gene regulatory networks. The role of these TFs in STB differentiation were confirmed in the hTSCs- and trophoblast organoid-derived STB. Together, our data provide valuable insights into the heterogeneity of human STB and represents a valuable resource for interpreting its associated pregnancy complications.
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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.
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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: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:In human, the functional placenta requires the proper differentiation of trophoblastic subtypes from the trophoblast stem cells (hTSCs). Although successful derivation of hTSCs from the early placentas and blastocysts, these hTSCs face ethical concerns and limited models for trophoblast-related disorders at later stage, such as preeclampsia. Here, we show that both hESCs and hiPSCs are able to be induced to the long-term and proliferative hTSCs under defined culture medium. These induced trophoblast stem cells (iTSCs) are comparable to the hTSC cell line derived from blastocyst in morphology, growth properties, specific genes expression, capacity of differentiating toward extravillous cytotrophoblast and syncytiotrophoblast, and patterns of transcriptome profile, chromatin accessibility and histone modification that are conducive to placenta development and maintenance of hTSCs. Notably, iTSCs meet four criteria defining "trophoblastic" including: expression of specific transcript factors, hypomethylation of ELF5 promoter, lack of expression of HLA-class I molecules and expression of the chromosome 19-encoded miRNA. Moreover, we reveal that addition of BMP4 or absence of H3K27 methyltransferases EZH1/2 could enhance the iTSCs generation. Our results suggest that human TS cells could be derived from human pluripotent stem cells, which expands the source of human TS cells avoiding ethic issues and provides a useful tool for researching placenta development and function, and modeling placenta-originated disorders.
2021-08-16 | GSE135694 | GEO
Project description:In human, the functional placenta requires the proper differentiation of trophoblastic subtypes from the trophoblast stem cells (hTSCs). Although successful derivation of hTSCs from the early placentas and blastocysts, these hTSCs face ethical concerns and limited models for trophoblast-related disorders at later stage, such as preeclampsia. Here, we show that both hESCs and hiPSCs are able to be induced to the long-term and proliferative hTSCs under defined culture medium. These induced trophoblast stem cells (iTSCs) are comparable to the hTSC cell line derived from blastocyst in morphology, growth properties, specific genes expression, capacity of differentiating toward extravillous cytotrophoblast and syncytiotrophoblast, and patterns of transcriptome profile, chromatin accessibility and histone modification that are conducive to placenta development and maintenance of hTSCs. Notably, iTSCs meet four criteria defining "trophoblastic" including: expression of specific transcript factors, hypomethylation of ELF5 promoter, lack of expression of HLA-class I molecules and expression of the chromosome 19-encoded miRNA. Moreover, we reveal that addition of BMP4 or absence of H3K27 methyltransferases EZH1/2 could enhance the iTSCs generation. Our results suggest that human TS cells could be derived from human pluripotent stem cells, which expands the source of human TS cells avoiding ethic issues and provides a useful tool for researching placenta development and function, and modeling placenta-originated disorders.
2021-08-16 | GSE135695 | GEO
Project description:In human, the functional placenta requires the proper differentiation of trophoblastic subtypes from the trophoblast stem cells (hTSCs). Although successful derivation of hTSCs from the early placentas and blastocysts, these hTSCs face ethical concerns and limited models for trophoblast-related disorders at later stage, such as preeclampsia. Here, we show that both hESCs and hiPSCs are able to be induced to the long-term and proliferative hTSCs under defined culture medium. These induced trophoblast stem cells (iTSCs) are comparable to the hTSC cell line derived from blastocyst in morphology, growth properties, specific genes expression, capacity of differentiating toward extravillous cytotrophoblast and syncytiotrophoblast, and patterns of transcriptome profile, chromatin accessibility and histone modification that are conducive to placenta development and maintenance of hTSCs. Notably, iTSCs meet four criteria defining "trophoblastic" including: expression of specific transcript factors, hypomethylation of ELF5 promoter, lack of expression of HLA-class I molecules and expression of the chromosome 19-encoded miRNA. Moreover, we reveal that addition of BMP4 or absence of H3K27 methyltransferases EZH1/2 could enhance the iTSCs generation. Our results suggest that human TS cells could be derived from human pluripotent stem cells, which expands the source of human TS cells avoiding ethic issues and provides a useful tool for researching placenta development and function, and modeling placenta-originated disorders.
2021-08-16 | GSE135693 | GEO
Project description:Human trophoblast stem cells (hTSCs) have emerged as a powerful tool for modeling the placental cytotrophoblast (CTB) in vitro. hTSCs were originally derived from CTBs of the first trimester or blastocyst-stage embryos in trophoblast stem cell medium (TSCM) that contains epidermal growth factor (EGF), the glycogen synthase kinase-beta (GSK3b) inhibitor CHIR99021, the transforming growth factor-beta (TGFb) inhibitors A83-01 and SB431542, valproic acid (VPA), and the Rho-associated protein kinase (ROCK) inhibitor Y27632. Here we show that hTSCs can be derived from CTBs isolated from the term placenta, using TSCM supplemented with a low concentration of mitochondrial pyruvate uptake inhibitor UK5099 and lipid-rich albumin (TUA medium). Notably, hTSCs could not be derived from term CTBs using TSCM alone, or in the absence of either UK5099 or lipid-rich albumin. Strikingly, hTSCs cultured in TUA medium for a few passages could be transitioned into TSCM and cultured thereafter in TSCM. hTSCs from term CTBs cultured in TUA medium as well as those transitioned into and cultured in TSCM thereafter could be differentiated to the extravillous trophoblast and syncytiotrophoblast lineages, and exhibited high transcriptome similarity with hTSCs derived from first trimester CTBs. We anticipate that these results will enable facile derivation of hTSCs from normal and pathological placentas at birth with diverse genetic backgrounds, and facilitate in vitro mechanistic studies in trophoblast biology.
2024-05-09 | GSE267112 | GEO