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- W4387396723 abstract "Endometriosis is an inflammatory disease characterized by the presence of tissue outside the uterus that resembles endometrium. We aim to apply single-cell RNA-sequencing (scRNA-seq) to identify molecular and cellular characteristics in the endometrium that give rise to endometriosis, across different menstrual phases in comparison with healthy controls. Using scRNA-Seq we studied 29 subjects with endometriosis across different stages of disease and compared them to 7 healthy controls, with both groups encompassing samples taken during different phases of the menstrual cycle. Endometrial tissue was processed to capture single cells, which were barcoded and sequenced using the 10x platform. Preprocessing of the data included alignment, demultiplexing and integration using Harmony for batch correction. We filtered for low transcript numbers and high mitochondrial ratio. Using canonical markers and semi-supervised annotation via SingleR, we identified major cell types and subtypes. Differential expression (DE) analysis was performed using MAST. Cell communication pathways between immune cells and tissue were identified using CellChat. We profiled 237,620 cells and identified 5 main cell groups consisting of stromal fibroblast, smooth muscle, endothelial, epithelial, and immune cells. Further analysis of immune cells revealed 18 sub-populations including uterine NK cells, T cells, monocytes, and macrophages. Epithelial cell populations comprise glandular, luminal, and ciliated cells. Comparing expression between endometriosis and controls revealed an upregulation of CXCL14, CCL20 in endometriosis in endothelial, epithelial, and stromal fibroblast cell types. Genes such as MMP7, PAEP and SFRP4 were DE in disease compared to control samples, regardless of phase in stromal fibroblast, endothelial and epithelial cells. Additionally, DE analysis of specific immune cell types, such as uterine NK cells, revealed an upregulation of GNLY and COTL1 in endometriosis, which may suggest differences in innate immune response. We discovered different communication landscapes in endometriosis compared to healthy individuals across different menstrual phases with pathways such as CSF3 and IL-6 being active in disease. We observed an upregulation of cytokine production, stress signal and pro-inflammatory pathways in disease in immune, stromal fibroblast, and epithelial cells. Enriched pathways in epithelial and ciliated cells related to migration and cell motility were upregulated in endometriosis cases. Cell communication analysis revealed a complex network of inflammatory pathways, with significant involvement of classical monocytes and NK cells." @default.
- W4387396723 created "2023-10-07" @default.
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- W4387396723 date "2023-10-01" @default.
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- W4387396723 title "ENDOMETRIAL SUBCELLULAR ALTERATIONS IN ENDOMETRIOSIS IDENTIFIED BY SINGLE-CELL ANALYSIS ACROSS THE MENSTRUAL CYCLE" @default.
- W4387396723 doi "https://doi.org/10.1016/j.fertnstert.2023.08.204" @default.
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