ArticleBiomarker research2024
Single-cell and spatial transcriptomics reveal alterations in trophoblasts at invasion sites and disturbed myometrial immune microenvironment in placenta accreta spectrum disorders.
Article in Biomarker research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Dysregulation of the Heparanase/TFPI-2/Heparan Sulfate Axis in Recurrent Pregnancy Loss.International journal of molecular sciences · 2026Article
- Single-cell and spatial transcriptomics identify SPP1 + trophoblast necroptosis as a potential contributor to late-onset preeclampsia via SPP1-CD44-mediated interaction with macrophages.Journal of translational medicine · 2026Article
- 3D imaging of the pregnant uterus reveals an extensively invasive mouse placenta and early CXCL12-CXCR4 requirement.bioRxiv : the preprint server for biology · 2026Article
- Placenta Accreta Spectrum: Diagnostic Challenges and Management Strategies.Diagnostics (Basel, Switzerland) · 2026Review
- A FOS/NFKB1-associated Hofbauer cell subset mediates placental niche dysregulation in early-onset fetal growth restriction.Frontiers in cell and developmental biology · 2026Article
- Insights into the maternal-fetal interface from spatial multi-omics.Frontiers in cell and developmental biology · 2026Review
- Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025Review
- Role of Inflammatory and Coagulation Biomarkers in Distinguishing Placenta Accreta from Placenta Previa and Associated Hemorrhage.Journal of clinical medicine · 2025Article
- Epidermal growth factor receptor in placental health and disease: pathways, dysfunction, and chemical disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- HIF1A facilitates hypoxia-induced changes in H3K27ac modification to promote myometrial contractility.Communications biology · 2025Article
- Advances in Prenatal Diagnosis of Placenta Accreta Spectrum.Medicina (Kaunas, Lithuania) · 2025Review
- Decreased plasma APOA1 levels are associated with increased severity of placenta accreta spectrum disorders: a nested case-control study.Frontiers in endocrinology · 2025Article
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11 authors.
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Abstract
backgroundPlacenta accreta spectrum disorders (PAS) are a severe complication characterized by abnormal trophoblast invasion into the myometrium. The underlying mechanisms of PAS involve a complex interplay of various cell types and molecular pathways. Despite its significance, both the characteristics and intricate mechanisms of this condition remain poorly understood.
methodsSpatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq), were performed on the tissue samples from four PAS patients, including invasive tissues (ST, n = 3; scRNA-seq, n = 4), non-invasive normal placenta samples (ST, n = 1; scRNA-seq, n = 2). Three healthy term pregnant women provided normal myometrium samples (ST, n = 1; scRNA-seq, n = 2). ST analysis characterized the spatial expression landscape, and scRNA-seq was used to identify specific cellular components in PAS. Immunofluorescence staining was conducted to validate the findings.
resultsST slices distinctly showed the myometrium in PAS was invaded by three subpopulations of trophoblast cells, extravillous trophoblast cells, cytotrophoblasts, and syncytiotrophoblasts, especially extravillous trophoblast cells. The pathways enriched by genes in trophoblasts, smooth muscle cells (SMC), and immune cells of PAS were mainly associated with immune and inflammation. We identified elevated expression of the angiogenesis-stimulating gene PTK2, alongside the cell proliferation-enhancing gene EGFR, within the trophoblasts of PAS group. Trophoblasts mainly contributed the enhancement of HLA-G and EBI3 signaling, which is crucial in establishing immune escape. Meanwhile, SMC regions in PAS exhibited upregulation of immunomodulatory markers such as CD274, HAVCR2, and IDO1, with CD274 expression experimentally verified to be increased in the invasive SMC areas of the PAS group.
conclusionsThis study provided information of cellular composition and spatial organization in PAS at single-cell and spatial level. The dysregulated expression of genes in PAS revealed a complex interplay between enhanced immune escape in trophoblasts and immune tolerance in SMCs during invasion in PAS. These findings will enhance our understanding of PAS pathogenesis for developing potential therapeutic strategies.
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