Fig. 4: Cell state alterations are coupled with a switch of dependency on epigenetics and lineage–specific transcription factors.
From: RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity
a Focused CRISPR library screening procedure using SK-N-AS cell lines derived from naïve and indisulam-resistant SK-N-AS tumor cells cultured for 3 weeks in the presence of absence of 250 nM of indisulam. b Dependency genes related to pre-mRNA splicing in naïve and resistant SK-N-AS cells with or without 250 nM of indisulam culture. c Ranked dependency genes encode transcriptional factors in naïve and resistant SK-N-AS cells with or without 250 nM of indisulam culture. Blue indicates MES TFs, and pink indicates ADRN TFs. P values (two-sided) generated by the MAGeCK-VISPR method. d–f Normalized counts of gRNAs for CDK9, PHOX2B and TBX2 in naïve and resistant SK-N-AS cells with or without 250 nM of indisulam culture (biological replicates, n = 4). p value calculated by the two-sided MAGeCK method. g Protein interaction network analysis (STRING: https://string-db.org) of epigenetic regulators that are selectively essential to naïve or indisulam-resistant tumors. h, i Normalized counts of gRNAs for PHF12 and ARID4B in naïve and resistant SK-N-AS cells with or without 250 nM of indisulam culture (biological replicates, n = 6). p-value calculated by the two-sided MAGeCK method. Source data are provided as a Source Data file.
