Genes uniquely expressed in human growth plate chondrocytes uncover a distinct regulatory network

In this study we explore the gene set that is selectively expressed in chondrocytes and therefore determines the unique properties and functions of cartilage tissue. Through identification of cartilage-selective transcription factors, lncRNAs, enhancers and protein-coding genes, we address the determinants of cartilage-selective gene expression, including interactions among the regulatory molecules and selectively active promoters, which define the pattern of gene expression and ultimately chondrocyte biology. Among 34 previously undescribed cartilage selective lncRNAs, one particular lncRNA was found to be co-expressed with and reciprocally regulated by SOX9, the master transcriptional regulator of chondrogenesis, revealing a new aspect of the regulation of the gene for this critical determinant of chondrocyte function. Finally, we relate cartilage-selective gene expression to the human and mouse skeletal disorders that result from mutations in many of the selectively regulated genes, providing clinical context to the basic biological discoveries. Identification of cartilage-selective genes in human fetal cartilage by RNA-seq