Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology.

  • Katja Lange (Creator)
  • Noortje Ijssennagger (Creator)
  • Ingrid T. Bijsmans (Creator)
  • Saskia W.C. van Mil (Creator)
  • Johan W. Jonker (Creator)
  • Guido Hooiveld (Creator)

Dataset

Description

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.
Date made available22 May 2017
PublisherWageningen University

Research Output

Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology

Bijsmans, I. T. G. W., Milona, A., Ijssennagger, N., Willemsen, E. C. L., Ramos Pittol, J. M., Jonker, J. W., Lange, K., Hooiveld, G. J. E. J. & van Mil, S. W. C., 2017, In : Biochimica et Biophysica Acta. Molecular Basis of Disease. 1863, 3, p. 687-700

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 8 Citations (Scopus)

    Cite this

    Lange, K. (Creator), IJssennagger, N. (Creator), Bijsmans, I. T. (Creator), van Mil, S. W. C. (Creator), Jonker, J. W. (Creator), Hooiveld, G. (Creator) (22 May 2017). Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology. Wageningen University.