Decidual natural killer cells promote extravillus trophoblast developmental pathways: evidence from trophoblast organoid co-cultures
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ABSTRACT:
PROVIDER: PRJNA1137979 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29897081_1.fastq.gz | Fastqsanger.gz | |||
| SRR29897081_2.fastq.gz | Fastqsanger.gz | |||
| SRR29897082_1.fastq.gz | Fastqsanger.gz | |||
| SRR29897082_2.fastq.gz | Fastqsanger.gz | |||
| SRR29897083_1.fastq.gz | Fastqsanger.gz |
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Project description:The placenta an essential extra-embryonic organ that supports the fetus throughout gestation. The interactions between the placenta and the maternal immune system during the first trimester have not been completely characterized, despite their close physical association and hem-allogeneic relationship to each other. The most abundant type of immune cell found in the uterus in the first trimester is the decidual natural killer cell (dNK). Despite their name, dNKs play supportive roles during pregnancy by remodelling uterine spiral arteries. We present evidence suggesting that the matrix metalloproteinases (MMPs) that dNKs secrete to promote this remodelling also drive placental development. This study was performed using a novel co-culture system of dNKs and trophoblast organoids, which are mini-organs that represent two to three different cell types of the human placenta. We found that co-cultures for one week led to significant (p=0.020) increases in organoid area. Through bulk RNA sequencing and immunohistochemical examinations we also observed significant decreases in trophoblast stemness markers, and upregulation of gene sets associated with extravillous trophoblast (EVT) development. These changes were accompanied by significant (p<0.001) increases in collagen subunit gene expression in the organoids, with simultaneous significant decreases (p<0.001) in the proportion of organoid area occupied by collagen as determined through Masson’s Trichrome. Cultures containing dNKs also contained significantly higher levels of MMP1, 3, 9, and 10 in their culture media, each of which can break down collagen. Collectively, these findings demonstrate that dNKs promote changes concordant with trophoblast differentiation towards EVTs and villous branching morphogenesis.
2024-08-31 | GSE272695 | GEO
Project description:The aim of this microarray experiment was to compare the overall transcriptomic profile of human placenta derived trophoblast organoid cultures with its tissue of origin, human placental villi. As the placental villi contains both trophoblast and stromal populations, we have included placenta derived stromal cultures in this comparison.
2018-11-28 | E-MTAB-6683 | biostudies-arrayexpress
Project description:Receptors of the KIR family on maternal Natural Killer cells in the decidua are believed to bind to Ligands such as HLA-C on trophoblast cells invading into the decidua from the placenta during early pregnancy. The resulting responses regulate the extent of trophoblast invasion. Genetic studies have implicated two members of the KIR family in particular as playing an important role: KIR2DL1 and KIR2DS1. The aim of this experiment was to determine what responses are generated when decidual NK cells bearing either KIR2DL1 or KIR2DS1 engage their HLA-C ligand.
2014-04-04 | E-MTAB-1784 | biostudies-arrayexpress
Project description:Trophoblast organoids offer a unique opportunity to study mechanisms orchestrating placental growth and development during pregnancy. However, many organoid cultures rely on extracellular matrix reagents that are highly variable and unable to be tuned to reflect in vivo tissues. Here we describe the first bioprinted placental organoid model, generated using first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol matrix. Bioprinted organoids were compared comprehensively to classic Matrigel-embedding using functional assays, immunofluorescence microscopy, transcriptomic and proteomic analyses. Organoids differentiated spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs), with bioprinted organoids driven towards EVT differentiation. Bioprinted organoids were exposed to inflammation and treated with aspirin or metformin to assess their effects on trophoblast organoid formation and viability. Further, we reversed the inside-out architecture of ACH-3P organoids by suspension culture. Organoid suspension caused STBs to form a syndecan-1+ outer layer on the periphery of organoids, reflecting placental tissue. Here, we present an alternative trophoblast organoid model with further tuning potential to reflect the placental microenvironment in physiological and pathological pregnancies.
2025-07-28 | PXD056796 | Pride
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
Project description:Decidual spiral arteriole (SpA) remodelling is essential to ensure optimal uteroplacental blood flow during human pregnancy. Decidual uterine natural killer cells and macrophages infiltrate the SpA and are proposed to initiate remodelling before colonisation by extravillous trophoblasts. Microarrays were used to measure the effect of extravillous trophoblasts conditioned medium on the transcriptome of human uterine microvascular endothelial cells.
2017-10-16 | E-MTAB-5467 | biostudies-arrayexpress
Project description:During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting immuno-acceptance of the fetal allograph. Global cross-talk between the trophoblast and the decidua has not been elucidated to date, and the current study used a functional genomics approach to investigate these paracrine interactions. Our data demonstrate a significant induction of pro-inflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune environment of the decidua to facilitate the process of implantation and assure an enriched cytokine/chemokine environment, while limiting mitotic activity of the stromal cells during the invasive phase of implantation. Keywords: Gene expression arrays in human stromal cells
2006-09-18 | GSE5809 | GEO
Project description:Natural killer cells (NKs) are abundant in the human decidua. Several diseases of poor placental development are associated with first pregnancies, and we thus looked to characterize differences in decidual NKs in first versus repeated pregnancies. We discovered a population unique to repeated pregnancies, which possesses a novel transcriptome and epigenetic signature, characterized with high expression levels of the receptors NKG2C and LILRB1. Activation of these receptors leads to increased production and secretion of IFNγ and VEGFa, the latter found to support vascular sprouting and trophoblast-tumor growth. We propose that this population represents NK “memory” of pregnancy, and have named these cells Pregnancy Trained decidual NK cells (PTdNKs). We further suggest that the precursors of PTdNKs are found in the endometrium. PTdNKs may prove useful in understanding and treating disorders of poor placentation.
2018-05-25 | GSE100636 | GEO
Project description:The implanting embryo and developing placenta interface with the endometrium through a multinuclear trophoblast layer, syncytiotrophoblast (STB), which plays critical barrier, transport, immunomodulatory and endocrine roles throughout pregnancy. Understanding trophoblast and endometrial biology has recently been accelerated through sophisticated stem cell and organoid models, however few studies have combined these models to explore maternal-embryo communication. Here, we combined organoid models of secretory phase and decidual endometrial glands with trophoblast stem cell-derived STB to investigate signalling from maternal glands to the developing placenta. Luminal secretions collected from endometrial organoids by centrifugation were added to STB cultures and transcriptome analysis revealed that both secretory phase and decidual organoid secretions had profound effects on STB gene expression, inducing 3279 and 2634 differentially expressed genes (DEG), respectively (padj<0.05, >50% ≥1 log2 fold change). Gene set enrichment analysis of shared DEG (1926 genes) suggested upregulation of immune signalling and downregulation of mitochondrial respiration. Secretory and decidual secretions led to increased basal and maximal respiration (p<0.01) but reduced respiratory spare capacity (p<0.05) in STB, while glycolytic activity was also increased (p<0.05) together with increased expression of rate-limiting glycolysis enzymes HK1, HK2, PFKP and PKM (padj<0.03). Integrating cytokine array analysis of organoid secretions with upstream regulator analysis of STB DEG identified VEGFA and CSF1 as secretory products that might regulate mitochondrial and glycolytic genes, respectively, whereas secreted LCN2 and IL1A were upstream of immunomodulatory genes. Regulation of both immunomodulatory and metabolic gene sets was predicted for secreted CSF1 and EGF. The findings suggest that STB is highly responsive to endometrial gland secretions, which induce metabolic reprogramming likely to result in a more glycolytic phenotype in vivo as well as stimulating STB to modulate maternal immune responses. Endometrial gland signals thus shape trophoblast development to support successful establishment of pregnancy.
2025-11-30 | GSE308529 | GEO
Project description:Transcriptional effect of trophoblast-decidual interactions.
2022-09-28 | GSE197810 | GEO