Single‐cell RNA sequencing in osteoarthritis

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(12)

Published: June 14, 2023

Osteoarthritis is a progressive and heterogeneous joint disease with complex pathogenesis. The various phenotypes associated each patient suggest that better subgrouping of tissues genotypes in different phases osteoarthritis may provide new insights into the onset progression disease. Recently, single-cell RNA sequencing was used to describe pathogenesis on high-resolution view surpassing traditional technologies. Herein, this review summarizes microstructural changes articular cartilage, meniscus, synovium subchondral bone are mainly due crosstalk amongst chondrocytes, osteoblasts, fibroblasts endothelial cells during progression. Next, we focus promising targets discovered by its potential applications target drugs tissue engineering. Additionally, limited amount research evaluation bone-related biomaterials reviewed. Based pre-clinical findings, elaborate clinical values for therapeutic strategies osteoarthritis. Finally, perspective future development patient-centred medicine therapy combining other multi-omics technologies discussed. This will cellular level field personalized therapeutics future.

Language: Английский

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Integrated single-cell RNA-seq analysis identifies immune heterogeneity associated with KRAS/TP53 mutation status and tumor-sideness in colorectal cancers

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 12, 2022

Background The main objective of this study was to analyze the effects KRAS/TP53 mutation status and tumor sideness on immune microenvironment colorectal cancer using integrated scRNA-seq data. Methods A total 78 datasets, comprising 42 treatment-naive tumors, 13 adjacent tissues 23 normal mucosa were included. Standardized Seurat procedures applied identify cellular components with canonical cell marks. batch-effect assessed corrected harmony algorithm. scMetabolism algorithm used for single-cell metabolic analysis. results clinical significance further validated immunofluorescent-staining TCGA-COAD datasets. Immune-infiltration scores bulk-RNA-seq data estimated ssGSEA. presto-wilcoxauc differentially enriched genes or pathways across different subgroups. Two-sided p-value less than 0.05 considered statistically significant. Results We refined landscape functional subtypes, especially T cells myeloid cells, mucosa, tissue. existence function two states exhausted CD8 + (Tex) subtypes in cancer, FOLR2 LYVE1 macrophages indicating unfavorable prognosis identified validated. diverse reshaped checkpoint ligands/receptors (ICLs/ICRs) expression pattern. Importantly, dual mutations significantly reduced major energy functions promoted cell-to-cell communications towards immunosuppression cancers. revealed LAG3, CD24-SIGLEC10 HBEGF-CD9 as potential therapeutic targets mutant Conclusions that underwent a gradual remodeling an enrichment immunosuppressive from regions Moreover, we heterogeneity tumor-infiltrating suggested may impair antitumor immunity by reducing metabolism reshaping interactions toward immunosuppression.

Language: Английский

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Single-cell multi-omics elucidates the role of RPS27-RPS24 fusion gene in osteosarcoma chemoresistance and metabolic regulation

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 25, 2025

Language: Английский

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Complement C1QC as a potential prognostic marker and therapeutic target in colon carcinoma based on single-cell RNA sequencing and immunohistochemical analysis

Bosnian Journal of Basic Medical Sciences, Journal Year: 2022, Volume and Issue: 22(6), P. 912 - 922

Published: June 23, 2022

Immune cell infiltration plays an essential role in the occurrence and development of colon cancer. However, main tumor-associated immune its gene regulation cancer still need to be further clarified order provide a new perspective for diagnosing treating this disease. For study, single-cell RNA sequencing (scRNA-seq) expression profiles TCGA data sets were first acquired from GEO database. Then, Seurat, Monocle, LIMMA, Clusterprofile, GSVA GSEABase algorithms used systematically examine data. Potential target drugs corresponding genes analyzed Drugbank database detected by molecular docking. Immunohistochemistry was assess level C1QC tissue microarray. Single analysis suggested that neutrophil activation might critical regulatory pathway macrophages population involved. Subsequent functional enrichment on differential may factor progression cancer, closely related survival patients. According drug prediction, palivizumab is targeted C1QC, docking demonstrated binds C1QC. Additionally, tissue-microarray based immunohistochemical showed highly expressed tissue, prognosis patients with high worse, age, lymphatic metastasis TNM stage (Tumor, Nodes Metastases). Our findings suggest regulate infiltration, which expected potential immunotherapy beneficial diagnosis

Language: Английский

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Single-cell RNA sequencing reveals the communications between tumor microenvironment components and tumor metastasis in osteosarcoma

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 11, 2024

Osteosarcoma is a common type of bone cancer characterized by poor prognosis due to its metastatic nature. The tumor microenvironment (TME) plays critical role in metastasis and therapy response. Therefore, our study aims explore the mechanism osteosarcoma, potentially opening new avenues for treatment.

Language: Английский

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Unlocking the tumor-immune microenvironment in osteosarcoma: insights into the immune landscape and mechanisms

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 18, 2024

Osteosarcoma has a unique tumor microenvironment (TME), which is characterized as complex comprising of bone cells, immune stromal and heterogeneous vascular structures. These elements are intricately embedded in mineralized extracellular matrix, setting it apart from other primary TMEs. In state normal physiological function, these cell types collaborate coordinated manner to maintain the homeostasis hematopoietic systems. However, pathological condition, i.e., neoplastic malignancies, tumor-immune (TIME) been shown promote cancer cells proliferation, migration, apoptosis drug resistance, well escape. The intricate dynamic system TIME osteosarcoma involves crucial roles played by various infiltrating complement system, exosomes. This complexity closely associated with evading surveillance, experiencing uncontrolled facilitating metastasis. this review, we elucidate interplay between diverse populations TIME, each contributing uniquely progression. From chondroblastic osteoblastic osteoclasts, myeloid lymphoid subsets, comprehensive single-cell analysis provides detailed roadmap ecosystem. Furthermore, summarize mutations, epigenetic mechanisms, vesicles that dictate immunologic landscape modulate osteosarcoma. perspectives clinical implementation immunotherapy therapeutic approaches for targeting also intensively discussed.

Language: Английский

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Comprehensive analysis of potential cellular communication networks in advanced osteosarcoma using single-cell RNA sequencing data

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 11, 2022

Osteosarcoma (OS) is a common bone cancer in children and adolescents, metastasis recurrence are the major causes of poor treatment outcomes. A better understanding tumor microenvironment required to develop an effective for OS. In this paper, single-cell RNA sequencing dataset was taken systematic genetic analysis, potential signaling pathways linked with osteosarcoma development were explored. Our findings revealed 25 clusters across 11 tissues, cell types including "Chondroblastic cells", "Osteoblastic "Myeloid "Pericytes", "Fibroblasts", "Proliferating osteoblastic "Osteoclasts", "TILs", "Endothelial "Mesenchymal stem "Myoblasts". The results Cell communication analysis showed 17 cellular networks "COLLAGEN pathway network", "CD99 "PTN "MIF "SPP1 "FN1 "LAMININ "FGF "VEGF "GALECTIN "PERIOSTIN "VISFATIN "ITGB2 "NOTCH "IGF "VWF "PDGF network". This research may provide novel insights into pathophysiology OS's molecular processes.

Language: Английский

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Ferroptosis and WDFY4 as novel targets for immunotherapy of lung adenocarcinoma

Aging, Journal Year: 2023, Volume and Issue: 15(18), P. 9676 - 9694

Published: Sept. 19, 2023

Background: Lung cancer exhibits the world's highest mortality rate among malignant cancers worldwide, thereby presenting a significant global challenge in terms of reducing patient mortality. In field oncology, targeted immunotherapy has emerged as novel therapeutic approach for lung cancer. This study aims to explore potential targets adenocarcinoma (LUAD) through analysis Ferroptosis Index (FPI) and Single Cell RNA-Sequencing (scRNA-seq) data. The findings this research can potentially offer valuable insights improving LUAD strategies informing clinical decision-making. Methods: Firstly, relationship between survival ferroptosis patients was analyzed by FPI. Subsequently, association infiltration regulation immune cells explored correlation statistics. Lastly, major infiltrating cell populations related pathways prognosis GSEA GSVA. To screen out core genes regulating populations, scRNA-seq data para-cancerous tissues were downloaded, followed clustering analysis, identification subpopulations, pseudotime single-cell GSVA pathway enrichment functional regulatory genes. Moreover, expression levels tissue microarray detected immunohistochemistry, its with verified. Finally, we used lentivirus WDFY4 transfect A549 cells. CCK-8, flow cytometry apoptosis detection, Scratch wound healing assay, Transwell migration Xenograft nude mice model, immunohistochemical other experimental methods biological effects on vitro vivo. Results: Survival FPI values revealed positive smaller longer overall survival. Immuno-infiltration that B most strongly associated ferroptosis. could promote activation more had long-term indicated population is one infiltrated LUAD. During later phases differentiation LUAD, there decrease ACAP1, LINC00926, TLR10, MS4A1, WDFY4, TRIM22 genes, whereas TMEM59, TP53INP1, METTL7A elevated. protein-protein interaction (PPI) network plays crucial role Immunohistochemical downregulation expression, which closely occurrence sites low exhibited poorer prognosis. Additionally, demonstrated overexpression inhibit proliferation metastasis while promoting apoptosis. It also confirmed growth Conclusions: results indicate improve patients, offering immunotherapeutic Besides, promotion upregulation have been shown induce populations. Furthermore, significantly vivo, highlighting target

Language: Английский

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Integrated Single-Cell RNA-Sequencing Analysis of Gastric Cancer Identifies FABP1 as a Novel Prognostic Biomarker

Journal of Oncology, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 16

Published: June 28, 2022

Gastric cancer (GC) is usually diagnosed in an advanced stage at the first visit due to atypical clinical symptoms. The low surgical resection rate and chemotherapy sensitivity result dismal survival. Therefore, it urgent develop novel biomarkers with high specificity accurately assess prognosis of GC patients. In present study, 3385 differentially expressed genes (DEGs) were obtained from single-cell RNA sequencing data specimens. Using unsupervised dimensionality reduction, we further found 3 subsets cells including gastric cells, plasmacytoid dendritic memory T cells. Based on cell clustering, explored key regulatory for progression by pseudo-time analysis functional enrichment analysis. According results, significant fatty acid-binding protein 1 (FABP1) verified was identified as hub gene progression. FABP1 shown be closely related long-term survival age diagnosis patients based TCGA (The Cancer Genome Atlas) database. To verify role GC, performed immunohistochemical (IHC) using tissue microarray that expression level higher tissues than adjacent tissues. Moreover, had a worse outcome. summary, our study revealed potential effective biomarker predicts unsatisfactory

Language: Английский

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Identification of novel prognostic biomarkers for osteosarcoma: a bioinformatics analysis of differentially expressed genes in the mesenchymal stem cells from single-cell sequencing data set

Translational Cancer Research, Journal Year: 2022, Volume and Issue: 11(10), P. 3841 - 3852

Published: Oct. 1, 2022

Background: Mesenchymal stem cells (MSCs) play a crucial role in osteosarcoma (OS) growth and progression. This study conducted bioinformatics analysis of single-cell ribonucleic acid sequencing data set explored the MSC-specific differentially expressed genes (DEGs) advanced OS. Methods: DEGs from GSE152048 was extracted using Seurat R package. These were then subjected to functional analysis, several key further identified underwent prognosis analysis. Results: A total 234 upregulated 280 downregulated between MSCs other cells, 188 158 osteoblastic cells. The Gene Ontology (GO) showed that specific enriched GO terms such as "collagen catabolic process", "positive regulation pathway-restricted SMAD protein phosphorylation", "osteoblast differentiation", "regulation release cytochrome c mitochondria" "interleukin-1 production". protein-protein interaction network Further, survival 20 with combined scores >0.94 revealed low expression ANXA1 (annexin A1) TPM1 (tropomyosin 1) associated shorter overall OS patients, while high FDPS (farnesyl pyrophosphate synthase), IFITM5 (interferon-induced transmembrane 5), FKBP11 (FKBP prolyl isomerase 11), SP7, SQLE (squalene epoxidase) patients. In we compared ANXA1, FDPS, IFITM5, FKBP11, SQLE, high-grade Further validation studies GSE42352 more than Conclusions: Our 7 hub derived may serve potential prognostic biomarkers for patients

Language: Английский

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