Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 523967
Title Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology.
Author(s) Lange, Katja; IJssennagger, Noortje; Bijsmans, Ingrid T.; Mil, Saskia W.C. van; Jonker, Johan W.; Hooiveld, Guido
Department(s) Human Nutrition (HNE)
Chair Nutrition Metabolism and Genomics
VLAG
Publication type Dataset
Publication year 2017
Keyword(s) GSE82111 - Mus musculus - PRJNA324071
Abstract Nuclear receptors (NRs) are ligand-activated transcription factors regulating a large variety of processes involved in reproduction, development, and metabolism. NRs are ideal drug targets. Immortalized cell lines recapitulate NR biology very poorly and primary cultures are laborious and require a constant need for donor material. There is a clear need for development of novel preclinical model systems that better resemble human physiology since technical uncertainty early in drug development is the cause of many preclinical drugs not reaching the clinic. Here, we studied whether organoids, mini-organs derived from the respective tissue’s stem cells, can serve as a novel (preclinical) model system to study NR biology and targeteability. We characterized mRNA expression profiles of the NR superfamily in mouse liver, ileum, and colon organoids. NR mRNA expression patterns were similar to the respective tissues, indicating their suitability for NR research. Metabolic NRs Fxrα, Lxrα, Lxrβ, Pparα, and Pparγ were responsive to ligands in an NR-dependent fashion, as demonstrated by regulation of expression and binding to endogenous target genes. Transcriptome analyses of wildtype colonic organoids stimulated with Rosiglitazone showed that lipid metabolism was the highest significant changed function, greatly mimicking the known function of PPARs and Rosiglitazone in vivo. In conclusion, our results demonstrate that organoids constitutes a versatile and promising in vitro system to study NR biology and targeteability.
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