Evidence map›Paper›PMID 39475639›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2024

A comprehensive transcriptome characterization of individual nuclear receptor pathways in the human small intestine.

Sam Willemsen, Fjodor A Yousef Yengej, Jens Puschhof, Maarten B Rookmaaker, Marianne C Verhaar, Johan van Es, Joep Beumer, Hans Clevers

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Sam Willemsen *Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.
Fjodor A Yousef Yengej *Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.
Jens PuschhofHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.
Maarten B RookmaakerUniversity Medical Centre Utrecht, Utrecht 3584 CX, The Netherlands.
Marianne C VerhaarUniversity Medical Centre Utrecht, Utrecht 3584 CX, The Netherlands.ORCID 0000-0002-3276-6428
Johan van EsHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.
Joep BeumerHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.
Hans CleversHubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.ORCID 0000-0002-3077-5582

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) 024.003.013 ZWK MDR
6 · The paper itself

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.

Indexed as

Intestine, SmallReceptors, Cytoplasmic and NuclearTranscriptomeEnterocytesGene Expression RegulationHumansLipid MetabolismLiver X ReceptorsOrganoidsPregnane X ReceptorReceptors, CalcitriolSignal TransductionLiver X ReceptorsPregnane X ReceptorReceptors, CalcitriolReceptors, Cytoplasmic and NuclearVDR protein, humanlipid absorptionnuclear receptorsorganoidssmall intestine

Identifiers

PMID39475639
PMCPMC11551338

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.