Dataset Information

Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing.

ABSTRACT: Tumors are complex ecosystems harboring multiple cell types which might play a critical role in tumor progression and treatment response. The endometrial epithelial cell identities and immune microenvironment of endometrial carcinoma (ECC) are poorly characterized. In this study, a cellular map of endometrial carcinoma was generated by profiling 30,780 cells isolated from tumor and paratumor tissues from five patients using single-cell RNA sequencing. 7 cell types in lymphocytes, 7 types in myeloid cells and 3 types in endometrial epithelial cells were identified. Distinct CD8⁺ T cell states and different monocyte-macrophage populations were discovered, among which exhausted CD8⁺ T cells and macrophages were preferentially enriched in tumor. Both CD8⁺ T cells and macrophages comport with continuous activation model. Gene expression patterns examination and gene ontology enrichment analysis of endometrial epithelial cells revealed 3 subtypes: stem-like cells, secretory glandular cells and ciliated cells. Overall, our study presents a view of endometrial carcinoma at single-cell resolution that reveals the characteristics of endometrial epithelial cells in the endometrium, and provides a cellular landscape of the tumor immune microenvironment.

SUBMITTER: Guo YE

PROVIDER: S-EPMC7993685 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing.

Guo Yu-E YE Li Yiran Y Cai Bailian B He Qizhi Q Chen Guofang G Wang Mengfei M Wang Kai K Wan Xiaoping X Yan Qin Q

Aging 20210110 5

Tumors are complex ecosystems harboring multiple cell types which might play a critical role in tumor progression and treatment response. The endometrial epithelial cell identities and immune microenvironment of endometrial carcinoma (ECC) are poorly characterized. In this study, a cellular map of endometrial carcinoma was generated by profiling 30,780 cells isolated from tumor and paratumor tissues from five patients using single-cell RNA sequencing. 7 cell types in lymphocytes, 7 types in myel ...[more]

PMID: 33429363

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Project description:PurposeThis study aimed to define the heterogeneity, spatial localization, and functional roles of immune cells in the mouse cornea using single-cell RNA sequencing (scRNA-seq) and immunofluorescent staining.MethodsEnriched mouse corneal immune cells (C57BL/6 strain, age 16-20 weeks) underwent single-cell RNA sequencing library preparation, sequencing, and analysis with Seurat, Monocle 3, and CellChat packages in R. Pathway analysis used Qiagen Ingenuity Pathway Analysis software. Immunostaining confirmed cell distribution.ResultsWe identified 14 distinct immune cell clusters (56% myeloid and 44% lymphoid). Myeloid populations included resident macrophages, conventional dendritic cells (cDC2s), Langerhans cells, neutrophils, monocytes, and mast cells. Additionally, lymphocyte subsets (B, CD8, CD4, γδT, natural killer, natural killer T, and group 2 innate lymphoid cells) were found. We also found three new subtypes of resident macrophages in the cornea. Trajectory analysis suggested a differentiation pathway from monocytes to conventional dendritic cells, resident macrophages, and LCs. Intercellular communication network analysis using cord diagram identified amyloid precursor protein, chemokine (C-C motif) ligands (2, 3, 4, 6, 7, 9, and 12), Cxcl2, Mif, Tnf, Tgfb1, Igf1, and Il10 as prominent ligands involved in these interactions. Sexually dimorphic gene expression patterns were observed, with male myeloid cells expressing genes linked to immune regulation (Egr1, Foxp1, Mrc1, and Il1rn) and females showing higher expression of antigen presentation genes (Clic1, Psmb8, and Psmb9). Finally, immunostaining confirmed the spatial distribution of these cell populations within the cornea.ConclusionsThis study unveils a diverse immune landscape in the mouse cornea, with evidence for cell differentiation and sex-based differences. Immunostaining validates the spatial distribution of these populations, furthering our knowledge of corneal immune function.

Project description:The pathogenesis of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains unclear, though increasing evidence suggests inflammatory processes play key roles. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) was used to decipher the immunometabolic profile in 4 ME/CFS patients and 4 heathy controls. We analyzed changes in the composition of major PBMC subpopulations and observed an increased frequency of total T cells and a significant reduction in NKs, monocytes, cDCs and pDCs. Further investigation revealed even more complex changes in the proportions of cell subpopulations within each subpopulation. Gene expression patterns revealed upregulated transcription factors related to immune regulation, as well as genes associated with viral infections and neurodegenerative diseases.CD4+ and CD8+ T cells in ME/CFS patients show different differentiation states and altered trajectories, indicating a possible suppression of differentiation. Memory B cells in ME/CFS patients are found early in the pseudotime, indicating a unique subtype specific to ME/CFS, with increased differentiation to plasma cells suggesting B cell overactivity. NK cells in ME/CFS patients exhibit reduced cytotoxicity and impaired responses, with reduced expression of perforin and CD107a upon stimulation. Pseudotime analysis showed abnormal development of adaptive immune cells and an enhanced cell-cell communication network converging on monocytes in particular. Our analysis also identified the estrogen-related receptor alpha (ESRRA)-APP-CD74 signaling pathway as a potential biomarker for ME/CFS in peripheral blood. In addition, data from the GSE214284 database confirmed higher ESRRA expression in the monocyte cell types of male ME/CFS patients. These results suggest a link between immune and neurological symptoms. The results support a disease model of immune dysfunction ranging from autoimmunity to immunodeficiency and point to amyloidotic neurodegenerative signaling pathways in the pathogenesis of ME/CFS. While the study provides important insights, limitations include the modest sample size and the evaluation of peripheral blood only. These findings highlight potential targets for diagnostic biomarkers and therapeutic interventions. Further research is needed to validate these biomarkers and explore their clinical applications in managing ME/CFS.

Project description:BackgroundSevere acute pancreatitis (SAP) is characterized by inflammation, with inflammatory immune cells playing a pivotal role in disease progression. This study aims to understand variations in specific immune cell subtypes in SAP, uncover their mechanisms of action, and identify potential biological markers for predicting Acute Pancreatitis (AP) severity.MethodsWe collected peripheral blood from 7 untreated SAP patients and employed single-cell RNA sequencing for the first time to construct a transcriptome atlas of peripheral blood mononuclear cells (PBMCs) in SAP. Integrating SAP transcriptomic data with 6 healthy controls from the GEO database facilitated the analysis of immune cell roles in SAP. We obtained comprehensive transcriptomic datasets from AP samples in the GEO database and identified potential biomarkers associated with AP severity using the "Scissor" tool in single-cell transcriptomic data.ResultsThis study presents the inaugural construction of a peripheral blood single-cell atlas for SAP patients, identifying 20 cell subtypes. Notably, there was a significant decrease in effector T cell subsets and a noteworthy increase in monocytes compared to healthy controls. Moreover, we identified a novel monocyte subpopulation expressing high levels of PPBP and PF4 which was significantly elevated in SAP. The proportion of monocyte subpopulations with high CCL3 expression was also markedly increased compared to healthy controls, as verified by flow cytometry. Additionally, cell communication analysis revealed insights into immune and inflammation-related signaling pathways in SAP patient monocytes. Finally, our findings suggest that the subpopulation with high CCL3 expression, along with upregulated pro-inflammatory genes such as S100A12, IL1B, and CCL3, holds promise as biomarkers for predicting AP severity.ConclusionThis study reveals monocytes' crucial role in SAP initiation and progression, characterized by distinct pro-inflammatory features intricately linked to AP severity. A monocyte subpopulation with elevated PPBP and CCL3 levels emerges as a potential biomarker and therapeutic target.

Dataset Information

Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing.

Publications

Phenotyping of immune and endometrial epithelial cells in endometrial carcinomas revealed by single-cell RNA sequencing.

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