Primary pancreatic acini were isolated as described in Panciera et al. 201618 (link) from rtTAM2; colYAP mice, or from rtTAM2 littermates as control (both male and females, 6-8 weeks old). Acini were seeded in neutralized rat tail collagen type I (Cultrex)/acinar culture medium (1:1)53 (link) and overlaid with acinar culture medium (Waymouth’s medium [Life Technologies] supplemented with 0.1% FBS [Life Technologies], 0.1% BSA, 0.2 mg/ml soybean trypsin inhibitor [SBTI], 1× insulin-transferrin-selenium-ethanolamine [ITS-X] [Life Technologies], 50 μg/ml bovine pituitary extract [BPE] [Life Technologies], 1μg/ml dexamethasone [Sigma], and antibiotics) supplemented with 0.5μg/ml doxycycline and DMSO or 10μM JQ1, as indicated. ADM events were counted 2-4 days after seeding. For EdU incorporation, 20μM EdU was added to culture medium for 90 min, then collagen cushions containing acini/ducts were extensively washed in PBS and fixed in 4% PFA for 20 min at RT. EdU staining was performed with Click-iT EdU Alexa Fluor 488 Imaging Kit (Thermo Fisher Scientific), according to manufacturer instructions. Total RNA was extracted with TRIzol Reagent (Invitrogen).