Analysis Tools
digestive/alimentary system
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• 12 days after a single TAM injection, mice show a significant increase in the number of mucin+ goblet cells in proximal jejunal crypts
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of AB/PAS+ goblet cells in proximal jejunal crypts
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• when mice are treated with TAM 24 h prior to crypt isolation, ISCs cultured in standard medium are 34.4% less capable of forming organoids, with resulting organoids showing a 40.5% increase in goblet cells and a 64.3% decrease in tdTomato+ cells per organoid relative to controls
• exogenous beta-hydroxybutyrate (beta-OHB), but not lactate (a Paneth niche-derived metabolite that sustains ISC function), restores the organoid-forming capacity and generation of tdTomato + clones and rescues the secretory lineage bias
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• 12 and >22 days after a single TAM injection, mice show a significant increase in the number of LYZ1+ Paneth cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls)
• as early 24 h after TAM injection, ISCs generate significantly greater numbers of tdTomato+ Paneth cells in jejunal sections
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of LYZ+ Paneth cells in proximal jejunal crypts
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• 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
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• when mice are fed a ketogenic diet (KTD) for 4 weeks, TAM-treated and then irradiated, the number of tdTomato+ crypts per mm jejunum is significantly higher than in chow-fed control mice, indicating enhanced regenerative output of tdTomato-labeled ISCs after injury
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• when mice are treated with TAM 1 day prior to radiation-induced intestinal epithelial injury, ISCs generate 5-fold less labeled tdTomato+ crypts with fewer Lgr5+ ISC-derived labeled progeny extending up crypt-villous units at 5 days post-radiation, and the overall number of surviving intact jejunal crypts is reduced by 2-fold
• oral administration of poly(lactic-co-glycolic acid) (PLGA) encapsulated beta-hydroxybutyrate (beta-OHB) nanoparticles or betaOHB oligomers partially rescues intestinal regeneration after radiation-induced damage
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) rescues the decline in ISC numbers and ISC function after radiation-induced injury
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endocrine/exocrine glands
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• 12 and >22 days after a single TAM injection, mice show a significant increase in the number of LYZ1+ Paneth cells in proximal jejunal crypts
• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls)
• as early 24 h after TAM injection, ISCs generate significantly greater numbers of tdTomato+ Paneth cells in jejunal sections
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of LYZ+ Paneth cells in proximal jejunal crypts
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• 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
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homeostasis/metabolism
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• mice treated with TAM 1 day prior to radiation-induced intestinal epithelial injury show impaired Lgr5+ ISC-mediated repair in jejunal crypts relative to controls
• oral administration of nanoparticle PLGA-encapsulated beta-OHB or betaOHB oligomers partially rescues intestinal regeneration after radiation-induced damage
• when mice are fed a ketogenic diet (KTD) for 4 weeks, TAM-treated and then irradiated, the number of tdTomato+ crypts per mm jejunum is significantly higher than in chow-fed controls, indicating enhanced regenerative output of tdTomato-labeled ISCs after injury
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) rescues the decline in ISC numbers and ISC function after radiation-induced injury
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cellular
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• 12 days after a single TAM injection, mice show a significant increase in the number of mucin+ goblet cells in proximal jejunal crypts
• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of AB/PAS+ goblet cells in proximal jejunal crypts
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• when mice are treated with TAM 24 h prior to crypt isolation, ISCs cultured in standard medium are 34.4% less capable of forming organoids, with resulting organoids showing a 40.5% increase in goblet cells and a 64.3% decrease in tdTomato+ cells per organoid relative to controls
• exogenous beta-hydroxybutyrate (beta-OHB), but not lactate (a Paneth niche-derived metabolite that sustains ISC function), restores the organoid-forming capacity and generation of tdTomato + clones and rescues the secretory lineage bias
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