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Toxoplasma gondii dictates placental trophoblast lineage specification through induction of decidual signaling cues [single nuclei multiome]

ABSTRACT: Toxoplasma gondii dictates placental trophoblast lineage specification through induction of decidual signaling cues [single nuclei multiome]

PROVIDER: PRJNA1158856 | ENA |

REPOSITORIES: ENA

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Toxoplasma gondii dictates placental trophoblast lineage specification through induction of decidual signaling cues [single nuclei multiome]

Project description:Pregnancy is a critical point of vulnerability to infection and other insults that could compromise proper fetal development. The placenta acts as a protective and nutrient-permeable barrier to most infectious agents, but a few are capable of bypassing its defenses. Remarkably little is known about how exposure to these select pathogens might impact ongoing placental development. Here we demonstrate thatToxoplasma gondii entirely misdirects the developmental program of trophoblast stem cells. Infection of progenitor cytotrophoblasts prevents fusion and differentiation to infection-resistant syncytiotrophoblast. Rather, T. gondii elicits a unique transcriptional identity that polarizes cytotrophoblasts to the infection-permissive extravillous trophoblast fate. Strong evidence of developmental disruption is found in multiple orthogonal models, including trophoblast stem cells, trophoblast organoids, and chorionic villi. Manipulation of cell fate by the parasite is most dramatic in trophoblast organoids, where we see robust outgrowth of HLA-G(+) extravillous trophoblasts. Collectively, these data show thatToxoplasmaantagonizes differentiation of an infection-resistant cell type by inducing formation of an infection-permissive cell type, therefore potentiating its own transmission to the fetus.

2025-09-01 | GSE276786 | GEO

Proteomic profiling of human decidual immune proteins during Toxoplasma gondii infection

Project description:A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (>1.2-fold cutoff, P＜0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic research identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.

2018-07-27 | PXD008448 | Pride

Single-cell transcriptomic analysis of decidual immune cell landscape in the occurrence of adverse pregnancy outcomes induced by Toxoplasma gondii infection

Project description:Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can lead to adverse pregnancy outcomes, particularly in early pregnancy. Previous studies have illustrated the landscape of decidual immune cells. However, the landscape of decidual immune cells in the maternal–fetal microenvironment during T. gondii infection remains unknown. In this study, we employed single-cell RNA sequencing to analyze the changes in human decidual immune cells following T. gondii infection. Our results showed that the proportion of 17 decidual immune cell clusters and the expression levels of 21 genes were changed after T. gondii infection. Differential gene analysis demonstrated that T. gondii infection induced the differential expression of 279, 312, and 380 genes in decidual NK, dMφ, and dT cells, respectively. Our findings first revealed that several previously unknown molecules in decidual immune cells changed following T. gondii infection. This result revealed that the function of maternal–fetal immune tolerance declined, whereas the killing ability of decidual immune cells enhanced, eventually contributing to the occurrence of adverse pregnancy outcomes. The results of this study provide a valuable resource for uncovering several novel molecules that play an important role in the occurrence of abnormal pregnancy outcomes induced by T. gondii infection.

2024-05-17 | GSE254302 | GEO

Human decidual macrophage clustering

Project description:First trimester decidual macrophages were clustered into three subpopulations by CCR2 and CD11c

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Multiome experiment from GLI3 KO brain organoids

Project description:To study the effect of GLI3 knockout on early brain organoid development, we collected single-cell multiome data from 18 day old brain organoids

2022-08-25 | E-MTAB-12002 | biostudies-arrayexpress

TBX5 KO multiome

Project description:TBX5 KO multiome

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10X Multiome AKSP

Project description:10X Multiome AKSP

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Expression data from CD11cHI and CD11cLO decidual macrophage populations.

Project description:Decidual macrophage populations, CD11cHI and CD11cLO cells were analyzed for expression profiles and unique characteristics. We used microarrays to detail the global program of gene expression and to determine differences between these two unique decidual macrophage populations.

2011-05-23 | GSE22342 | GEO

Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells

Project description:A successful pregnancy requires many physiological adaptations from the mother, including the establishment of tolerance towards the semiallogeneic fetus. Innate lymphoid cells (ILCs) have arisen as important players in immune regulation and tissue homeostasis at mucosal and barrier surfaces. Dimensionality reduction and transcriptomic analysis revealed the presence of two novel CD56Bright decidual ILCs, C10 and C2, that express divergent levels of Eomes. We found that decidual C10, C2, and cNKs correlated highly with previously identified first trimester decidual dNKs (dNK1-3). Functional analysis revealed polyfunctional profiles that depend on the nature of the stimulus, with a preference for IFNgamma and VEGF production. Overall, our data suggests persistence of pregnancy-specific decidual innate lymphocytes across pregnancy.

2020-01-24 | GSE129555 | GEO

Multiome scRNA- and scATAC-seq for SHH treated brain organoids

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