library_construction_protocol: Each screen was performed in triplicate with independent transductions. For each replicate, 24 x 10^6  SNRPN-2A-GFP VP64dCas9VP64 (maternal) or dCas9KRAB (paternal) iPSCs were dissociated using Accutase (Stemcell Tech, 7920) and transduced in suspension across five matrigel-coated 15-cm dishes in mTesR (Stemcell Tech 85850) supplemented with 10 μM Rock Inhibitor (Y-27632, Stemcell Tech, 72304). Cells were transduced at a MOI of 0.2 to obtain one gRNA per cell and ~430-fold coverage of the gRNA library. The medium was changed to fresh mTesR without Rock Inhibitor 18-20 h after transduction. Antibiotic selection was started 30 h after transduction by adding 1 μg/mL puromycin (Sigma, P8833) directly to the plates without changing the medium. The cells were fed daily and passaged as necessary maintaining library coverage until harvest. Cells were harvested for sorting 9 d after transduction of the gRNA library for all screens. Cells were washed once with 1x PBS, dissociated using Accutase, filtered through a 30 μm CellTrics filter (Sysmex, 04-004-2326) and resuspended in FACS Buffer (0.5% BSA (Sigma, A7906), 2 mM EDTA (Sigma, E7889) in PBS). Before sorting, an aliquot of 4.8 x 10^6 cells were taken to represent a bulk unsorted population. The highest and lowest 10% of cells were sorted based on GFP expression and 4.8 x 10^6 cells were sorted into each bin. Sorting was done with a SH800 FACS Cell Sorter (Sony Biotechnology).