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000294378 1001_ $$aWillemsen, Sam$$b0
000294378 245__ $$aA comprehensive transcriptome characterization of individual nuclear receptor pathways in the human small intestine.
000294378 260__ $$aWashington, DC$$bNational Acad. of Sciences$$c2024
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000294378 520__ $$aNuclear receptors (NRs) are widely expressed transcription factors that bind small, lipophilic compounds and regulate diverse biological processes. In the small intestine, NRs are known to act as sensors that control transcriptional responses to endogenous and exogenous signals, yet their downstream effects have not been characterized extensively. Here, we investigate the activation of six different NRs individually in human intestinal organoids using small molecules agonists. We observe changes in key enterocyte functions such as lipid, glucose, and amino acid absorption, the regulation of electrolyte balance, and drug metabolism. Our findings reinforce PXR, LXR, FXR, and PPARα as regulators of lipid absorption. Furthermore, known hepatic effects of AHR and VDR activation were recapitulated in the human small intestine. Finally, we identify unique target genes for intestinal PXR activation (ERG28, TMEM97, and TM7SF2), LXR activation (RAB6B), and VDR activation (CA12). This study provides an unbiased and comprehensive transcriptomic description of individual NR pathways in the human small intestine. By gaining a deeper understanding of the effects of individual NRs, we might better harness their pharmacological and therapeutic potential.
000294378 536__ $$0G:(DE-HGF)POF4-314$$a314 - Immunologie und Krebs (POF4-314)$$cPOF4-314$$fPOF IV$$x0
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000294378 650_7 $$2Other$$alipid absorption
000294378 650_7 $$2Other$$anuclear receptors
000294378 650_7 $$2Other$$aorganoids
000294378 650_7 $$2Other$$asmall intestine
000294378 650_7 $$2NLM Chemicals$$aReceptors, Cytoplasmic and Nuclear
000294378 650_7 $$2NLM Chemicals$$aReceptors, Calcitriol
000294378 650_7 $$2NLM Chemicals$$aLiver X Receptors
000294378 650_7 $$2NLM Chemicals$$aVDR protein, human
000294378 650_7 $$2NLM Chemicals$$aPregnane X Receptor
000294378 650_2 $$2MeSH$$aHumans
000294378 650_2 $$2MeSH$$aIntestine, Small: metabolism
000294378 650_2 $$2MeSH$$aReceptors, Cytoplasmic and Nuclear: metabolism
000294378 650_2 $$2MeSH$$aReceptors, Cytoplasmic and Nuclear: genetics
000294378 650_2 $$2MeSH$$aTranscriptome
000294378 650_2 $$2MeSH$$aReceptors, Calcitriol: metabolism
000294378 650_2 $$2MeSH$$aReceptors, Calcitriol: genetics
000294378 650_2 $$2MeSH$$aLiver X Receptors: metabolism
000294378 650_2 $$2MeSH$$aLiver X Receptors: genetics
000294378 650_2 $$2MeSH$$aLiver X Receptors: agonists
000294378 650_2 $$2MeSH$$aOrganoids: metabolism
000294378 650_2 $$2MeSH$$aSignal Transduction
000294378 650_2 $$2MeSH$$aLipid Metabolism: genetics
000294378 650_2 $$2MeSH$$aEnterocytes: metabolism
000294378 650_2 $$2MeSH$$aPregnane X Receptor: metabolism
000294378 650_2 $$2MeSH$$aPregnane X Receptor: genetics
000294378 650_2 $$2MeSH$$aGene Expression Regulation: drug effects
000294378 7001_ $$aYengej, Fjodor A Yousef$$b1
000294378 7001_ $$0P:(DE-He78)04965ffa43dd78e7f52259c5fceffefa$$aPuschhof, Jens$$b2$$udkfz
000294378 7001_ $$aRookmaaker, Maarten B$$b3
000294378 7001_ $$00000-0002-3276-6428$$aVerhaar, Marianne C$$b4
000294378 7001_ $$avan Es, Johan$$b5
000294378 7001_ $$aBeumer, Joep$$b6
000294378 7001_ $$00000-0002-3077-5582$$aClevers, Hans$$b7
000294378 773__ $$0PERI:(DE-600)1461794-8$$a10.1073/pnas.2411189121$$gVol. 121, no. 45, p. e2411189121$$n45$$pe2411189121$$tProceedings of the National Academy of Sciences of the United States of America$$v121$$x0027-8424$$y2024
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