Fig. 4

CRISPRi screens identify Wnt-regulated lncRNAs loci that modify cell growth in a context-dependent manner. a Schematic representation of CRISPRi screens conducted using xenograft tumors in vivo and in cultured cells in vitro to identify functional Wnt-regulated lncRNAs in RNF43-mutant pancreatic cancer. b Comparison of FDR from in vivo and in vitro screens. The dashed lines represent the threshold (FDR = 10%) for calling hits by gene-associated FDR. lncRNA hits are colored based on their FDR from both in vivo and in vitro screens. c Comparison of sgRNA fold change after in vivo and in vitro screens. Each gene is colored based on hits calling from B. d sgRNAs targeting LINC00263 are significantly depleted from both in vivo and in vitro screens. e sgRNAs targeting ABHD11-AS1 are significantly enriched only from the in vivo screen. f sgRNAs targeting AP000487.1 are significantly enriched only from the in vitro screen. The normalized counts of 5 sgRNAs targeting the TSS of LINC00263, ABHD11-AS1, and AP000487.1 are shown before and after both screens in d–f. g sgRNAs targeting the TSS of LINC00263 reduce the expression of LINC00263 and SCD. h sgRNAs targeting LINC00263 reduce HPAF-II cell growth in vitro. Cell numbers were counted at days 6, 10, 14, and 16 after seeding and normalized to the seeding density. i sgRNAs targeting SCD reduce HPAF-II cell growth in vitro. sgNTC does not affect cell growth. Cell numbers were counted at days 6, 10, and 14 after seeding and normalized to the seeding density. NTC, non-targeting control