In vitro cartilage tissues following overexpression of TFs

Cartilage plays a crucial role in skeletal development and function, and abnormal development contributes to genetic and age-related skeletal disease. Compromises to the integrity of joint-lining articular cartilage in particular lead to debilitating chronic degenerative diseases including osteoarthritis. To better understand how human articular cartilage develops in vivo, we jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femora at 2 fetal timepoints. We used these multiomic data to predict transcription factor-based regulatory networks that are important for articular chondrocyte differentiation. We developed a human pluripotent stem cell platform for interrogating the function of predicted transcription factors during chondrocyte differentiation and identified new biological roles for CREB5. We expect new regulatory networks we uncovered using multiomic data to be important for promoting cartilage health and treating disease, and our platform to be a useful tool for studying cartilage development in vitro.