Single-Cell Transcriptomics of Proliferative Phase Endometrium: Systems Analysis of Cell–Cell Communication Network Using CellChat

Abstract

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell–cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell–cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell–cell interactome by assessing the gene expression of receptor–ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell–cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell–cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell–cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell–cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.

Role of dysregulated macrophage subpopulation ratios and functional changes in the development of coronary atherosclerosis

“…56 In contrast, Angpt 1 can antagonize the effects of Angpt 2. 57 Angpt 1 exhibits a protective effect against saturated fatty acidinduced preadipocyte apoptosis and endoplasmic reticulum stress. 58 Our cellular communication results indicate that Angpt1, which has anti-inflammatory effects, is mainly expressed by six clusters of macrophages at week 0 of a high-fat diet (Figure S7), while Angpt2, which has pro-inflammatory effects, is expressed at week 16 (Figures S11 and S12).…”

“…It is closely linked to cardiac valve calcification, atherosclerosis, inflammation and vascular remodeling 56 . In contrast, Angpt 1 can antagonize the effects of Angpt 2 57 . Angpt 1 exhibits a protective effect against saturated fatty acid‐induced preadipocyte apoptosis and endoplasmic reticulum stress 58 .…”

Comprehensive bulk and single-cell transcriptome profiling give useful insights into the characteristics of osteoarthritis associated synovial macrophages

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Clinicopathological role of Cyclin A2 in uterine corpus endometrial carcinoma: Integration of tissue microarrays and ScRNA-Seq

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