Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Single-Cell RNA Sequencing Reveals the Cellular and Molecular Characterization of Discoid Meniscus

ABSTRACT: Discoid meniscus is a morphological abnormality with a higher prevalence in Asian populations (15%-20%) compared to American populations (3%-5%). Although most patients are asymptomatic, discoid meniscus are more susceptible to injury than normal menisci. Currently, our understanding of its pathogenesis and pathophysiology remains limited. In this study, we employed single-cell RNA sequencing to analyze four cases of discoid meniscus (including three lateral and one medial) and three control meniscus samples, revealing differences in cell types and extracellular matrix composition between the two groups. Our findings indicate that the activation of BMP and HIF1A signaling pathways, along with the inactivation of the Wnt signaling pathway, may contribute to discoid meniscus development, with the transcription factor SCX identified as a key regulatory factor. These findings provide new insights into the pathogenesis of discoid meniscus and may offer a theoretical foundation for future therapeutic strategies.

INSTRUMENT(S): computer, 10x Genomics, Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Song-po Shen

PROVIDER: E-MTAB-15232 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

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Single-Cell RNA Sequencing Reveals the Cellular and Molecular Characterization of Discoid Meniscus

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