• TAM-treated mice show a progressive loss of OLFM4+ intestinal stem cells (ISCs) and early progenitors (seen both at 10-12 days and at 17+ days but not at 5-7 days after a single TAM injection), along with an increase in the numbers of Paneth cells and goblet cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a modest increase in the fraction stem cells (35.34% vs 22.96% in controls), fewer transit-amplifying progenitors (18.40% vs 25.73% in controls) and a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls), along with a weakened Lgr5+ stemness signature in ISCs but only minor effects on proliferation and apoptosis
• 12 days after a single TAM injection, crypt cells show induction of Atoh1 mRNA transcripts and reduction of Hes1 mRNA transcripts by ISH
• 17 days after a single TAM injection, no change in the proliferation or apoptosis of ISCs and progenitors is observed, and small intestine length, crypt depth, and numbers of chromogranin A+ enteroendocrine cells in jejunal crypts are normal
• TAM-treated mice show reduced numbers of H3K27ac-positive and Notch intracellular domain (NICD)-positive crypt cell nuclei, indicating increased class I histone deacetylase (HDAC) activity and less Notch signaling
• TAM treatment followed by administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of H3K27ac-positive and NICD-positive crypt cell nuclei to wild-type numbers