Fig. 3 | Nature Communications

Fig. 3

From: In vivo reprogramming drives Kras-induced cancer development

Fig. 3

Repression of acinar cell enhancers by in vivo reprogramming. a Microarray analysis in the pancreas of C-OSKM mice given Dox for 3 days. b A qRT-PCR for acinar cell-related genes and ADM-related genes after Dox treatment for 24 h in the pancreas of C-OSKM mice. Data are presented as the mean of technical triplicates. The mean expression level of wild-type samples was set to 1 for Amy, Mist1, Ptf1a, and CK19. For Tff1 and Muc5ac, the mean expression level of Dox 24 h samples was set to 1. c ChIP-seq analysis for H3K27ac in the pancreas of C-OSKM mice. Note that H3K27ac deposition is substantially reduced at acinar cell-related transcription factors (Ptf1a and Mist1). d Super enhancers (SEs) in the pancreas of C-OSKM mice. Note that Dox OFF-specific SEs show significant reduction in H3K27ac deposition in Dox ON pancreas. The number of SEs is decreased after Dox treatment for 3 days. e Dox OFF-specific SE-related gene expressions are significantly suppressed by OSKM induction. ***p < 0.001, Mann–Whiteney U-test. f Forced expression of an acinar cell-related transcription factor (Ptf1a or Mist1) inhibits OSKM-induced ADM formation. EGFP expression represents the expression of either Ptf1a or Mist1. Note that most EGFP-expressing cells are negative for CK19 while the control EGFP-expressing cells often costained with CK19. Scale bars, 50 μm. The ratio of CK19-positive cells in EGFP-positive cells of 10 independent images are shown in a box-and-whisker plot. Solid lines in each box indicate the median. Bottom and top of the box are lower and upper quartiles, respectively. Whiskers extend to ±1.5 interquartile range (IQR). ***p < 0.001, Mann–Whiteney U-test. g Super enhancers (SEs) in caerulein-treated pancreas. Note that caerulein treatment causes reduction in H3K27ac deposition at SEs that are repressed by OSKM induction

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