Fig. 3: Inhibition of necroptotic and apoptotic cell death restores transdifferentiation capability of pancreatic acinar cells from KRASG12D TAK1ΔAc mice.
a, b Experimental design to study cell death induction in primary pancreatic acinar cells grown in 2D cell culture upon treatment with TNF (100 ng/ml). Immunobloting analysis in pancreatic acinar cells isolated from the indicated mice. The experiment was done once with one mouse per genotype. c, d H&E staining and IHC of α-Amylase and CK17/19 on pancreatic tissue sections from 18-week-old mice with the indicated genotype and quantification of healthy pancreas tissue (Normal), ADM and PanIN-1 of the same animals (n = 6 mice per genotype). e, f Experimental design to study the transdifferentiation capability of pancreatic acinar cell explants in 3D collagen matrices isolated from the indicated mice. Representative images are shown by bright-field microscopy and after H&E staining. Intact duct-like structures are highlighted with red arrowheads. The experiment was done with acinar explants from 2 different mice per genotype. g, h H&E staining and IHC of α-Amylase and CK17/19 of pancreatic tissue sections from 52-week-old mice with the indicated genotype and quantification of healthy pancreas tissue (Normal), ADM and PanIN-1 of the same mice (n = 5 mice per genotype). i, j Array comparative genomic hybridization (aCGH) analysis of pancreas tissue (ADM, PanIN and PDAC areas) from 52-week-old WT (n = 3), KRASG12D (n = 5) and KRASG12D TAK1/CASP8ΔAC RIPK3-/- (n = 5) mice. The pancreatic tissue of individual transgenic mice was hybridized against the pancreatic tissue of age-matched WT mice and analyzed by aCGH. The q-arm of each chromosome is shown and chromosome numbers are indicated. Dark horizontal bars within the symbolized chromosomes represent G bands. Chromosomal deletions (loss) are indicated in red and amplifications (gain) in blue. Five mice per analyzed genotype are labeled by horizontal-colored bars. Mice with PDAC are labeled with a green star. Map of pancreatic cancer associated genes located in the chromosomal gain and loss regions detected by aCGH analysis is depicted in (j). Vertical lines next to each gene locus represent individual mice. Source data are provided in the Source Data file.
