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| Status |
Public on May 22, 2017 |
| Title |
Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
Microarray analysis was performed on colonic organoids isolated from wildtype and intestinal epithelium-specific PPARγ mice that were treated with the PPARγ agonist Rosiglitazone or vehicle for 24 hrs.
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| Contributor(s) |
Lange K, IJssennagger N, Bijsmans IT, van Mil SW, Jonker JW, Hooiveld GJ |
| Citation(s) |
27956139 |
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| Submission date |
Jun 01, 2016 |
| Last update date |
May 24, 2017 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (10)
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| GSM2183601 |
colonic organoid, PPARγ KO, Rosiglitazone, replicate 1 |
| GSM2183602 |
colonic organoid, PPARγ KO, Rosiglitazone, replicate 2 |
| GSM2183603 |
colonic organoid, PPARγ KO, vehicle, replicate 1 |
| GSM2183604 |
colonic organoid, PPARγ KO, Rosiglitazone, replicate 3 |
| GSM2183605 |
colonic organoid, wild type, Rosiglitazone, replicate 1 |
| GSM2183606 |
colonic organoid, PPARγ KO, vehicle, replicate 2 |
| GSM2183607 |
colonic organoid, wild type, Rosiglitazone, replicate 2 |
| GSM2183608 |
colonic organoid,wild type, vehicle, replicate 1 |
| GSM2183609 |
colonic organoid, wild type, Rosiglitazone, replicate 3 |
| GSM2183610 |
colonic organoid,wild type, vehicle, replicate 2 |
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| Relations |
| BioProject |
PRJNA324071 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE82111_RAW.tar |
42.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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