Fig. 1: Targeted CRISPR-Cas9 dropout screens identify unique genetic vulnerabilities in patient-derived colon CSC-enriched spheroids.

A Experimental workflow of the targeted CRISPR-Cas9 dropout screens. B Composition of the Epi-Drug sgRNA library. C Validation of the endonuclease activity of Cas9 protein with two sgRNAs targeting an individual gene METTL3 in two Cas9-expressing spheroids. D Distribution of sgRNA reads per gene at indicated time points post-transfection. E Volcano plots showing the genes significantly depleted in POP92 and POP66. Genes with P value < 0.01 were considered as essential for colon CSC-enriched spheroids propagation in vitro (threshold indicated by dashed line). Depleted genes were overlapped with a public CSC database, with matching genes highlighted in red. Source data of all genes are provided in Supplementary Tables S1 and S2.