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

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. ATAC-seq was executed in pediatric hMSC-osteoblasts, hFOB 1.19 cells (hFOBs), osteoclasts, and primary chondrocytes in order to study the heritability enrichment of bone mineral density in regulatory regions of a diverse number of cell types. ATAC-seq in hFOBs was also used for identifying regulatory regions to be targeted in a paired CRISPRi screen in hFOBs.