Single‐cell RNA sequencing reveals the cell types heterogenicity of human discoid lateral meniscus cells

Abstract

Discoid lateral meniscus (DLM) is more prone to injury than a normally shaped meniscus. No study has compared the gene expression and cell heterogeneity between discoid and normal menisci. We aimed to identify specific cell clusters and their marker genes in discoid meniscus, thereby providing a theoretical basis for the treatment and etiology of DLM. ScRNA-seq was used in DLM and osteoarthritis lateral meniscus (OAM) cells to identify cell subsets and their gene signatures. Pseudo-time analysis and immunohistochemical staining were used to investigate the temporal and spatial distribution of DLM-specific clusters. ScRNA-seq identified nine clusters originating from DLM and OAM, composed of seven empirically defined populations and two novel populations specific to DLM, namely, the prehypertrophic chondrocyte 2 (PreHTC-2) and regulatory chondrocyte (RegC-2) populations. Single-cell trajectory showed that RegC-2 and PreHTC-2 were mainly distributed in a specific cell fate, with the PreHTC-2 marker gene HAPLN1 highly expressed at the end of this fate. Immunohistochemical staining showed that HAPLN1 + cells were mainly distributed in the white zone of DLM.Matrix metalloproteinase (MMP) variants were expressed in DLM and OAM, with MMP2 highly expressed in OAM-dominant cell clusters, while MMP3 was highly expressed in DLM-dominant cell clusters. We concluded that two novel cell clusters including PreHTC-2 were identified using single-cell sequencing, which were mainly distributed in the white areas of DLM. Differentiated MMP expression in the trajectory may be a possible mechanism of DLM formation.

Older age and the presence of intrameniscal signs are risk factors for nonsurgical treatment failure of symptomatic intact discoid lateral meniscus

“…Therefore, they proposed that the discoid meniscus is a structural, rather than a morphological, variant. Reduced number, structural abnormalities, and disorganization of collagen fibers make them more prone to tear and degenerate [2, 22, 24].…”

Chinese Experts Consensus and Practice Guideline on Discoid Lateral Meniscus

“…20,80,81 Except for the morphological and anatomical abnormalities above, the circular collagen fibers are disintegrated and disorganized, the nutrient vessels are sparse, and mucoid degeneration often occurs. These pathological characteristics changes may be the main reason DLM is prone to lesions, degeneration, postoperative retear, and poor healing 1,3,[9][10][11][12][13][14][15][16]82,83 (Grade E).…”

Single‐cell RNA sequencing in osteoarthritis

“…The specific cell clusters contributing to meniscus aberrant degeneration demonstrated a novel mechanism of meniscus degeneration. Another study showed FCs (fibrochondrocytes) populations in meniscus cells, with COL1A1 highly expressed, increased gelatinases such as MMP2, which may contribute to cartilage homeostasis in the physiological status 102–104 …”

“…Another study showed FCs (fibrochondrocytes) populations in meniscus cells, with COL1A1 highly expressed, increased gelatinases such as MMP2, which may contribute to cartilage homeostasis in the physiological status. [102][103][104] Among the meniscus zones, the red zone is rich in blood vessels.…”