Bioinformatics and single-cell CRISPRi-based screen reveals effector genes and implicates multi-tissue etiology for BMD [Capture-C]

To nominate identify tissues relevant to the etiology of bone mineral density we generated ATAC-seq in pediatric hMSC-osteoblasts, hFOB 1.19 cells (hFOBs), osteoclasts, and primary chondrocytes. Leveraging the results of this experiment, we designed a CRISPRi screen in hFOBs with scRNA-seq expression read out. The targets selected for the screen were informed by newly generated Capture-C and bulk RNA-seq from hFOBs. Overall design: hFOB 1.19 cells were differentiated at 39.5°C for 5 days prior to collection for sequencing.