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The Plk4 OE ESC line was first transduced with lentivirus carrying Cas9-EGFP ( Plk4 OE , Cas9 mESC ) and subsequently with a lentivirus library of single-guide RNAs (sgRNAs), in which each mouse gene was represented by approximately 10 unique sgRNAs 38 (~180,000 sgRNAs total), and cultured in the presence or absence (control) of doxycycline for 9 further days following the 4 th day post transduction (Supplementary Fig
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