Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USA.
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Sci Rep. 2024 Oct 31;14(1):26208. doi: 10.1038/s41598-024-76539-y.
Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the affected bone. These lesions harbor somatic mutations in IDH and driving expression of a mutant Idh1 in Col2 expressing cells in mice causes an enchondromatosis phenotype. Here we compared growth plates from E18.5 mice expressing a mutant Idh1 with control littermates using single cell RNA sequencing. Data from Col2 expressing cells were analysed using UMAP and RNA pseudo-time analyses. A unique cluster of cells was identified in the mutant growth plates that expressed genes known to be upregulated in enchondromas. There was also a cluster of cells that was underrepresented in the mutant growth plates that expressed genes known to be important in longitudinal bone growth. Immunofluorescence showed that the genes from the unique cluster identified in the mutant growth plates were expressed in multiple growth plate anatomic zones, and pseudo-time analysis also suggested these cells could arise from multiple growth plate chondrocyte subpopulations. This data supports the notion that a subpopulation of chondrocytes become enchondromas at the expense of contributing to longitudinal growth.
软骨瘤是一种常见的骨肿瘤，在软骨瘤病中可能会出现多个病变，这与受影响骨骼的畸形有关。这些病变在 IDH 中存在体细胞突变，并在表达 Col2 的细胞中驱动突变型 Idh1 的表达，导致软骨瘤病表型。在这里，我们使用单细胞 RNA 测序比较了表达突变型 Idh1 的 E18.5 小鼠和对照同窝仔鼠的生长板。使用 UMAP 和 RNA 伪时间分析对表达 Col2 的细胞的数据进行了分析。在突变型生长板中鉴定出一个独特的细胞簇，这些细胞表达已知在软骨瘤中上调的基因。在突变型生长板中也存在一个细胞簇表达在纵向骨生长中重要的基因，其表达水平较低。免疫荧光显示，在突变型生长板中鉴定出的独特细胞簇的基因在多个生长板解剖区域中表达，伪时间分析还表明这些细胞可能来自多个生长板软骨细胞亚群。该数据支持这样一种观点，即软骨细胞的亚群为了纵向生长而成为软骨瘤。
