Extended Data Fig. 1: SMARCA5 is a specific regulator of PDAC initiation.
a, Results from a CRISPR KO screening22 showing the relative representation of sgRNAs targeting different chromatin remodelers in a PDAC cell line. b, FPKM of marker genes in mCherryneg-acinar cells (see Method for details). n = 2 mice with 3 technical replicates each. One dot represents the average of the three technical replicates. Short horizontal lines indicate the mean. c, Western blotting indicating SMARCA5 and SMARCA4 depletion after sgRNA treatment. d, RT-qPCR showing depletion efficiencies of sgRNA-treated PDAC cells. e, ATAC-seq signals at chromatin regions more accessible in tumor than acinar (n = 59735) in the mouse PDAC cell line treated with another set of sgRNAs, in relation to Fig. 1a. f, ChIP-seq reads for SMARCA4 and SMARCA5 on chromatin regions that are shown in Fig. 1a. g, ATAC-seq signals at chromatin regions more accessible in tumor than acinar which are bound by SMARCA5 (right) or SMARCA4 (left). h, The numbers of overlapping ATAC-seq peaks regulated by either SMARCA4 or SMARCA5 in PDAC cell line. i, ATAC-seq signal at chromatin regions shared by tumor and acinar cells (n = 39586). j, SMARCA5-regulated peaks in “806” cells, with Smarca5 KO rescued with either WT SMARCA5 (SMARCA5WT) or enzymatically dead SMARCA5 (SMARCA5K211R). k, ATAC-seq signals at indicated chromatin regions in the mouse PDAC cell line “Scf” treated with indicated sgRNAs. l, Representative IF images of SMARCA5, amylase and KRT19. m, Representative IHC staining of SMARCA5. l and m, Scale bar, 20 μm. n and o, Box plots showing quantification of SMARCA5 signals in pancreatic cells. The box in box plot shows the interquartile range, spanning from the first quartile to the third quartile. The line inside the box represents the median, while the whiskers extend from the box to the minimum and maximum values of the dataset. For n, Acinar: n = 91 cells; ADM: n = 503 cells; PanIN: n = 224 cells; Tumor: n = 333 cells. For o, Acinar: n = 45 cells; ADM: n = 101 cells; PanIN: n = 121 cells; Tumor: n = 207 cells.
