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Proteogenomic and V(D)J Analysis of Human Decidual T cells Highlights Unique Transcriptional Programming and Clonal Distribution [VDJ-seq]

ABSTRACT: Immunological tolerance towards the semi-allogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface, however, their repertoire and subset programming is still poorly understood. Utilizing emerging scRNA-seq technologies we simultaneously obtained transcript, limited protein, and receptor repertoire at the single-cell level, from decidual and matched maternal peripheral T cells. In agreement with previous work, we find that the decidua maintains a tissue-specific distribution of T cells compared to the periphery. We find that decidual T cells maintain a unique transcriptome programming, characterized by restraint of inflammatory pathways by overexpression of negative regulators. Furthermore, we show little clonal overlap between the decidua and periphery, suggesting minimal ongoing traffic between these scites. Overall, our data demonstrate the power of multi-omic analysis in revealing regulation of fetal-maternal immune co-existence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE192558 | GEO | 2023/04/26

REPOSITORIES: GEO

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Multiomic analysis reveals decidual-specific transcriptional programing of MAIT cells

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2021-09-07 | GSE183421 | GEO

The role of chorionic PGRMC2 and HLA-G in maintaining immune homeostasis at the chorio-decidual interface

Project description:The chorio-decidual interface (CDi) is formed by chorion trophoblasts (CTCs) and immune cell-rich decidua (DECs) cells. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating innate immune homeostasis at this maternal-fetal interface interface were investigated.

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Gene expression profiling of mouse uterine decidua isolated on morning of day 8 of pregnancy

Project description:Placenta development involves complex molecular and cellular interactions between the maternal endometrium and the developing embryo, however, it is not clear what are the precise mechanisms regulating this maternal-fetal crosstalk. Using genetic and cell biological approaches, we have demonstrated that Ras-related C3 botulinum toxin substrate 1 (Rac1), a maternal factor expressed in decidual cells and is markedly elevated in mouse decidua on days 7 and 8 of gestation, regulates the secretory pathways that mediate stromal-endothelial and stromal-trophoblast crosstalk within a narrow temporal window during placenta development. Our study revealed that ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that RAC1 signaling regulates the expression of genes involved in angiogenesis and vesicle trafficking. Consequently, the Rac1-null decidual cells exhibited impaired secretory functions that led to poor vascularization of the uterus and abnormal trophoblast expansion and placentation.

2017-02-09 | GSE70446 | 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

Gene expression profile of decidual macrophages and different in vitro M1 and M2 macrophage populations

Project description:Uterine (decidual) macrophages (M) are believed to play an important role in fetal tolerance during pregnancy, but the factors that regulate them are not known. In this study we investigated the potential role of several factors (M-CSF, GM-CSF, IL-4/13, IL-10, progesterone and estradiol) to drive the differentiation and polarization of human decidual M by using an in vitro M differentiation model. To estimate the similarity of the in vitro differentiated M with decidual M, we used the present gene expression array. The array consisted of 420 M-related genes, including 100 genes highly regulated in decidual M based on the gene expression profile previously reported (Gustafsson et al, 2008, PLoS ONE. 3(4): e2078). The analysis focused on the 100 decidual M-associated genes. Comparative expression analysis of CD14+ cells isolated from blood (3 samples) or decidua (3 samples) from pregnant women, CD14+ cells isolated from non-pregnant women (14 samples) and different types of in vitro-generated macrophages (55 samples). A total of 75 samples were anlayzed.

2011-11-22 | E-GEOD-30595 | biostudies-arrayexpress

Single-cell RNA-seq to decipher the subpopulations of human decidual leukocytes in normal and RSA pregnancies

Project description:Maternal fetal immune tolerance is a biological event that plays a key role in pregnancy. In particular, the mechanism by which the maternal immune system does not exclude the semi-identical antigen of the fetus has not been fully answered so far. The most serious result of the maternal fetal immune tolerance balance is the recurrent spontaneous abortion (RSA). The fetus is rejected by the mother in the early pregnancy and cannot continue to develop in the uterus. Based on these scientific questions, we used single-cell sequencing technology to analyze nearly 30,000 leukocytes in the decidua of normal and RSA. A total of 13 immune cell subsets were found, of which dNK cells were more prominent, The lineage differentiation pathway of dNK cells was excavated, and the pathological role of dNK differentiation abnormality in the occurrence of RSA was analyzed. Our results deepen our understanding of the differentiation and function of human decidual leukocytes, especially dNK cells. We clearly recognize that the immune system has dynamic changes compared with normal pregnancy under pathological conditions, which is likely to occur in RSA. The important factors, we expect our results to provide a new basis for RSA's immune diagnosis and treatment strategy.

2021-07-20 | GSE130560 | GEO

Reconstructing the human first trimester fetal-maternal interface using single cell transcriptomics - Smartseq 2 data

Project description:To explore the interactions between the range of maternal and fetal placental cell types present, we profiled the transcriptomes of more than 50,000 single cells from matched first trimester samples of maternal blood and decidua, as well as fetal cells from the placenta itself. This part contains RNA-seq of Decidua cells using Smartseq 2

2019-08-21 | E-MTAB-6678 | biostudies-arrayexpress

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Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface

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2011-11-15 | E-GEOD-31680 | biostudies-arrayexpress

Transcription profiling of human decidual macrophages

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