Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE133449 | GEO | 2020/02/26
REPOSITORIES: GEO
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Project description:Meniscus degeneration is one of the manifestations of knee osteoarthritis, but its specific molecular mechanism is still not very clear. We used Wuzhishan pig's anterior cruciate ligament resection to prepare meniscus degeneration models, and applied gene chip technology to detect the expression of differential genes in the degenerated meniscus tissue. The study detected a total of 893 differentially expressed genes, mainly related to hormones, apoptosis, inflammation and other mechanisms, and analyzed that TRP channels may play a key role. All in all, we have established a reliable animal model of meniscus degeneration and found that meniscus degeneration involves several possible molecular mechanisms, which provide molecular targets for future treatment of the disease.
2020-08-13 | GSE156132 | GEO
Project description:Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue engineering are hindered by a lack of understanding of meniscus cell biology and a poorly defined meniscus cell phenotype. This study utilized bulk RNA-sequencing to identify unique and overlapping transcriptomic profiles in cartilage, inner and outer zone meniscus tissue, and passaged inner and outer zone meniscus cells. The greatest transcriptomic differences were identified when comparing meniscus tissue to monolayer cultured cells (> 4,600 differentially expressed genes (DEGs)) and meniscus tissue to cartilage (> 3,100 DEGs). While zonal differences exist within the meniscus tissue (205 DEGs between inner and outer zone meniscus tissue), meniscus resident cells are more similar to each other than to either cartilage or monolayer meniscus cells. Additionally, we identified and validated LUM and PRRX1 as potential markers for meniscus tissue and ACTA2, FSTL1, SFRP2, and TAGLN as novel markers for meniscus cell dedifferentiation. Our data contribute significantly to the current characterization of meniscus cells and provide an important foundation for future work in meniscus cell biology, regenerative medicine, and tissue engineering.
2024-11-10 | GSE275100 | GEO
Project description:There is a need to clarify the role of the meniscus in knee OA which may be aided by the identification of biomarkers that reflect the molecular events involved in the tissue degradation. This is of particular importance in the early stages of the degenerative processes, a crucial phase when it might still be possible to interfere with disease progression before tearing and critical loss of meniscal function occurs. One way to achieve this goal is exploratory proteomics by mass spectrometry (MS), which has the potential to analyse the proteome of complex samples. Thus, our aim was to gain new knowledge about the molecular processes within the human meniscus by comparing the proteomic profiles of both the lateral and medial meniscus from healthy controls, subjects with mild signs of joint degeneration, and patients with end-stage knee OA, using a non-targeted MS approach operating in data-independent acquisition (DIA) mode. For the research purpose six groups were established: medial and lateral menisci from control donors (n=12), medial and lateral menisci from donors with mild signs of joint degeneration (n=13) and medial and lateral menisci from end-stage knee OA patients (n=12).
2024-04-03 | PXD042122 | Pride
Project description:Objectives: To identify novel gene transcripts and biological processes in meniscus from patients with and without osteoarthritis (OA). Methods: We used microarrays to identify gene transcripts differentially expressed in meniscus tissues obtained from OA and non-OA patients (N=12 each). Real-time PCR was performed on selected gene transcripts. Biological processes and gene networking was examined computationally. Transcriptome signatures from OA and non-OA meniscus were mapped with 37 previously published gene transcripts differentially expressed between healthy and OA cartilage to evaluate how meniscus gene expression relates to cartilage with this disease. Results: We identified 168 gene transcripts that were significantly differentially expressed between OA (75 elevated, 93 repressed) and non-OA samples (≥1.5-fold). Among these, CSN1S1, COL10A1, WIF1, SPARCL1 and DEFA3 were the most prominent gene transcript elevated in OA meniscus and POSTN, VEGFA, CEMIP, COL6A3 and SOX11 were repressed in OA meniscus. Gene transcripts elevated in OA meniscus represented response to external stimuli, cell migration and localization while those repressed in OA meniscus represented histone deacetylase activity and skeletal development. Numerous long lncRNAs were differentially expressed between the two samples. When segregated by OA-associated gene transcripts, we observed three distinct clustering patterns of OA and non-OA meniscus. Conclusions: These data provide novel evidence for a role of epigenetically regulated histone deacetylation in meniscus tears as well as expression of lncRNAs. Patient clustering based on OA-associated gene transcripts confirmed that the meniscus in OA knees exhibited OA phenotype while injured meniscus demonstrated some signs towards OA.
2017-12-27 | GSE98918 | GEO
Project description:Analysis of gene expression in E16 mouse meniscus, articular cartilage, and cruciate ligaments Limbs were dissected from E16 CD-1 mice. Samples were frozen in OCT and cryosectioned. Meniscus, articular carilage, and cruciate ligament were isolated using laser capture microdissection. Total RNA was isolated from these tissues, amplified, and gene expression was analyzed using microarrays. Three biological replicates were analyzed for each tissue type. Total RNA extracted from E16 mouse meniscus, articular cartilage, and cruciate ligaments
2013-10-01 | E-GEOD-47799 | biostudies-arrayexpress
Project description:Discoid lateral meniscus (DLM) is more prone to injury than a normally shaped meniscus. Our previous study successfully identified the different cell types and their corresponding marker genes in meniscus tissues, but there was no study comparing the gene expression and cell heterogenicity of discoid meniscus with normal meniscus.
2023-12-06 | GSE162767 | GEO
Project description:In this study, we have tested the variation in gene expression signatures in human injured meniscus with age and degree of chondrosis in the knee. We found several genes that were differentially regulated with each of these factors and they represent important biological pathways in osteoarthritis research. Total RNA obtained from isolated injured meniscus tissues from patients undergoing arthroscopic partial meniscectomy.
2013-03-18 | E-GEOD-45233 | biostudies-arrayexpress
Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.
2015-03-06 | E-GEOD-66635 | biostudies-arrayexpress
Project description:Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA-Sequencing of non-degenerated and degenerated CEP cells were performed. Methods: Human lumbar CEP cells from degenerated (Thompson Grade ≥ 4) and non-degenerated (Thompson Grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA-Sequencing. Genes identified from bulk RNA-Sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA-Sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples. Results: Bulk RNA-Sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|Fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA-Sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA-Sequencing dataset showed that progenitor cell clusters from both samples were enriched in “non-degenerated” genes, but not “degenerated” genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction. Conclusions: This thorough analysis using RNA-Sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.
2024-01-10 | GSE242040 | GEO
Project description:Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA-Sequencing of non-degenerated and degenerated CEP cells were performed. Methods: Human lumbar CEP cells from degenerated (Thompson Grade ≥ 4) and non-degenerated (Thompson Grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA-Sequencing. Genes identified from bulk RNA-Sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA-Sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples. Results: Bulk RNA-Sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|Fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA-Sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA-Sequencing dataset showed that progenitor cell clusters from both samples were enriched in “non-degenerated” genes, but not “degenerated” genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction. Conclusions: This thorough analysis using RNA-Sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration.
2024-01-10 | GSE242443 | GEO