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@ARTICLE{Willemsen:294378,
author = {S. Willemsen and F. A. Y. Yengej and J. Puschhof$^*$ and M.
B. Rookmaaker and M. C. Verhaar and J. van Es and J. Beumer
and H. Clevers},
title = {{A} comprehensive transcriptome characterization of
individual nuclear receptor pathways in the human small
intestine.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {121},
number = {45},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DKFZ-2024-02211},
pages = {e2411189121},
year = {2024},
abstract = {Nuclear 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.},
keywords = {Humans / Intestine, Small: metabolism / Receptors,
Cytoplasmic and Nuclear: metabolism / Receptors, Cytoplasmic
and Nuclear: genetics / Transcriptome / Receptors,
Calcitriol: metabolism / Receptors, Calcitriol: genetics /
Liver X Receptors: metabolism / Liver X Receptors: genetics
/ Liver X Receptors: agonists / Organoids: metabolism /
Signal Transduction / Lipid Metabolism: genetics /
Enterocytes: metabolism / Pregnane X Receptor: metabolism /
Pregnane X Receptor: genetics / Gene Expression Regulation:
drug effects / lipid absorption (Other) / nuclear receptors
(Other) / organoids (Other) / small intestine (Other) /
Receptors, Cytoplasmic and Nuclear (NLM Chemicals) /
Receptors, Calcitriol (NLM Chemicals) / Liver X Receptors
(NLM Chemicals) / VDR protein, human (NLM Chemicals) /
Pregnane X Receptor (NLM Chemicals)},
cin = {D300},
ddc = {500},
cid = {I:(DE-He78)D300-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39475639},
doi = {10.1073/pnas.2411189121},
url = {https://inrepo02.dkfz.de/record/294378},
}