CROPSeq of Putative AD- and PSP-associated cis-Regulatory Regions in iPSC-derived Neurons and Microglia

We performed a pooled CRISPRi screen (CROP-seq) and genome editing to validate 19 genetic variants prioritized from massively parallel reporter assays to screen 5,706 polymorphisms from genome-wide association studies for both Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP) across 11 distinct loci. This allowed us to pinpoint regulatory targets in a cell-type specific manner. sgRNAs were created targeting putative cis-regulatory regions and were transfected into iPSC-derived iNeurons and iMicroglia containing CRISPRi machinery. These were then collected for 10X sequencing using the CROPseq method.