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Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression.

ABSTRACT: Objective: Osteoarthritis (OA) is the most common chronic degenerative joint disease, which represents the leading cause of age-related disability. Here, this study aimed to depict the intercellular heterogeneity of OA synovial tissues. Methods: Single-cell RNA sequencing (scRNA-seq) data were preprocessed and quality controlled by the Seurat package. Cell cluster was presented and cell types were annotated based on the mRNA expression of corresponding marker genes by the SingleR package. Cell-cell communication was assessed among different cell types. After integrating the GSE55235 and GSE55457 datasets, differentially expressed genes were identified between OA and normal synovial tissues. Then, differentially expressed marker genes were overlapped and their biological functions were analyzed. Results: Totally, five immune cell subpopulations were annotated in OA synovial tissues including macrophages, dendritic cells, T cells, monocytes and B cells. Pseudo-time analysis revealed the underlying evolution process in the inflammatory microenvironment of OA synovial tissue. There was close crosstalk between five cell types according to the ligand-receptor network. The genetic heterogeneity was investigated between OA and normal synovial tissues. Furthermore, functional annotation analysis showed the intercellular heterogeneity across immune cells in OA synovial tissues. Conclusion: This study offered insights into the heterogeneity of OA, which provided in-depth understanding of the transcriptomic diversities within synovial tissue. This transcriptional heterogeneity may improve our understanding on OA pathogenesis and provide potential molecular therapeutic targets for OA.

SUBMITTER: Liu W

PROVIDER: S-EPMC8784753 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most frequent and aggressive pancreatic tumor characterized by high metastatic risk and special tumor microenvironment. To comprehensively delineate the complex intra-tumoral heterogeneity and the underlying mechanism during metastatic lesions malignant progression, single-cell RNA sequencing (scRNA-seq) was employed. PCA and TSNE were used for dimensionality reduction analysis and cell clustering. Find All Markers function was used to calculate differential genes in each cluster, and Do Heatmap function was used to plot the distribution of differential genes in each cluster. GSVA was employed to assign pathway activity estimates to individual cells. Lineage trajectory progression was inferred by monocle. CNV status was inferred to compare the heterogeneity among patients and subtypes by infercnv. Ligand-receptor interactions were identified by CellPhoneDB, and regulons network of cells was analyzed by SCENIC. Through RNA-sequencing of 6236 individual cells from 5 liver metastatic PDAC lesions, 10 major cell clusters are identified by using unbiased clustering analysis of expression profiling and well-known cell markers. Cells with high CNV level were considered as malignant cells and pathway analyses were carried out to highlight intratumor heterogeneity in PDAC. Pseudotime trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. The complex cellular communication suggested potential immunotherapeutic targets in PDAC. Regulon network identified multiple candidates for promising cell-specific transcriptional factors. Finally, metastatic-related genes expression levels and signaling pathways were validated in bulk RNA Sequencing data. This study contributed a comprehensive single-cell transcriptome atlas and contributed into novel insight of intratumor heterogeneity and molecular mechanism in metastatic PDAC.

Project description:Hand photography has been used in a number of studies to determine the presence and severity of hand osteoarthritis (HOA). The aim of this study was to present age and gender specific prevalences of HOA diagnosed by this method.Six thousand three hundred forty three photographs (from 3676 females and 2667 males aged 40-96) were scored for hand osteoarthritis by a 0-3 grade (0?=?no evidence of OA, 1?=?possible OA, 2?=?definite OA and 3?=?severe OA) for each of the three main sites, distal interphalangeal joints (DIP), proximal interphalangeal joints (PIP) and thumb base (CMC1). An aggregate score of 0-9 was thus obtained (HOASCORE) to reflect the severity of HOA in each case.DIP joints were most commonly affected, followed by the thumb base and the PIP joints. Having definite DIP joint OA starts at a younger age compared with the other two sites, and there is a marked female preponderance in the age groups from 55 to 69, but after 70 the gender differences are less marked and the prevalence is fairly stable. PIP joint prevalence also indicates a female preponderance from 60 to 79. Thumb base OA has a more marked female preponderance and a rising prevalence thoughout life. The prevalence of individuals with no evidence of photographic OA (HOASCORE?=?0) drops from 88% to 57% between the age categories 40-49 and 50-54 and decreased to 33% in the 70-74 age group with a slower decline after that age. DIP and PIP prevalence were strongly associated with each other with an OR of 16.6(12.8-21.5),p?<?0.001 of having definite OA at the other site. This was less marked for the thumb base with an OR of 2.2(1.8-2.7, p?<?0.001), and 2.7(2.0-3.5, p?<?0.001) of having definite DIP or PIP HOA respectively.The prevalence of hand OA in DIP, PIP and thumb base joints obtained by the photographic HOASCORE method is higher in women and increases after the age of fifty. These results are in line with those obtained by clinical examination and radiography. The advantage of the method lies in easy applicability and low cost.

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Single-Cell Profiles of Age-Related Osteoarthritis Uncover Underlying Heterogeneity Associated With Disease Progression.

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