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Status |
Public on Nov 29, 2005 |
Title |
Gene regulatory networks along the small intestinal crypt-villus axis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Genes encoding transcription factors function as hubs in gene regulatory networks because they encode DNA-binding proteins, which bind to promoters that carry their binding sites. In the present work we have studied gene regulatory networks defined by genes with transcripts belonging to different mRNA abundance classes in the small intestinal epithelial cell. The focus is the rewiring that occurs in transcription factor hubs in these networks during the differentiation of the small intestinal epithelial cell while it migrates along the crypt-villus axis and during its development from a fetal endodermal cell to a mature adult villus epithelial cell. We have generated transcriptome data for mouse small intestinal villus, crypt and fetal intestinal epithelial cells. In addition we have generated metabolome data from crypt and villus cells. Our results show that the intestinal crypt transcription factor hubs that are rewired during differentiation are involved in the cell cycle process (E2F, NF-Y) and stem cell maintenance (c-Myc). In contrast the villi are dominated by a HNF-4 villus hub, which is rewired during differentiation by the addition of network genes with relevance for lipoprotein synthesis and lipid absorption. Moreover, we have identified a villus NF-kB hub, which was revealed by comparison of the villus and endoderm transcriptomes. The rewiring of the NF-kB villus hub during intestinal development reflects transcriptional activity established by host and microflora interactions. To aid in the mining of our results we have developed a web portal (http://gastro.imbg.ku.dk/mousecv/) allowing easy linkage between the transcriptomic data, biological processes and functions. Keywords: Cell type comparison
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Overall design |
Four different sample categories were analyzed.
1) Small intestinal crypts isolated form 12-weeks old C57BL/6 mice. These samples are in triplicates.
2) Small intestinal villi isolated form 12-weeks old C57BL/6 mice. These samples are in triplicates.
3) Embryonic day 12 mesenchyme. These samples are in quadruplicate. each sample is derived from a pool of mesenchymes (10-40)
4) Embryonic day 12 endoderm. These samples are in quadruplicate. each sample is derived from a pool of endoderms (10-40)
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Contributor(s) |
Stegmann A, Troelsen JT, Olsen J |
Citation(s) |
16868071 |
Submission date |
Aug 29, 2005 |
Last update date |
Jan 08, 2019 |
Contact name |
Jorgen Olsen |
E-mail(s) |
jolsen@sund.ku.dk
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Phone |
+45 30304085
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Organization name |
University of Copenhagen
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Department |
Department of Cellular and Molecular Medicine
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Street address |
Blegdamsvej 3
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City |
Copenhagen |
ZIP/Postal code |
DK2770 |
Country |
Denmark |
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Platforms (2) |
GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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Samples (14)
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Relations |
BioProject |
PRJNA92733 |