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Series GSE67634 Query DataSets for GSE67634
Status Public on Aug 24, 2015
Title Altered interactions between the gut microbiome and colonic mucosa precede polyposis in APCMin/+ mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Mutation of the adenomatous polyposis coli (APC gene), an early event in the adenoma-carcinoma sequence, is present in 70-80% of sporadic human colorectal adenomas and carcinomas. To test the hypothesis that mutation of the APC gene alters microbial interactions with host intestinal mucosa prior to the development of polyposis, culture-independent methods (targeted qPCR assays and Illumina sequencing of the 16S rRNA gene V1V2 hypervariable region) were used to compare the intestinal microbial composition of 30 six-week old C57BL/6 APCMin/+ and 30 congenic wild type (WT) mice. The results demonstrate that similar to 12-14 week old APCMin/+ mice with intestinal neoplasia, 6 week old APCMin/+ mice with no detectable neoplasia, exhibit an increased relative abundance of Bacteroidetes spp in the colon. Parallel mouse RNA sequence analysis, conducted on a subset of proximal colonic RNA samples (6 APCMin/+, 6 WT) revealed 130 differentially expressed genes (DEGs, fold change ≥ 2, FDR <0.05). Hierarchical clustering of the DEGs was carried out by using 1-r dissimilarity measurement, where r stands for the Pearson correlation, and Ward minimum variance linkage, in order to reduce the number of input variables. When the cluster centroids (medians) were included along with APC genotype as input variables, analysis of variance and covariance (ANCOVA) with stepwise variable selection, selected two of seven mouse gene clusters, in addition to APC genotype, as significantly associated (p = 0.011 and p = 0.004) with the increased relative abundance of Bacteroidetes spp. One of the two clusters includes several downregulated genes encoding immunoglobulin variable regions and non-protein coding RNAs. These results support the concept that mutation of the APC gene alters colonic-microbial interactions prior to polyposis. It remains to be determined whether interventions directed at ameliorating dysbiosis in APCMin/+mice, such as through probiotics, prebiotics or antibiotics, could reduce tumor formation.
Overall design Comparing the differential gene expressions in proximal colonic mucosal samples from 6 six-week-old female Apc Min/+ and 6 six-week-old female WT mice
Contributor(s) Son J, Khair S, Pettet DW, Ouyang N, Tian X, Zhang Y, Zhu W, Mackenzie GG, Robertson CE, Ir D, Frank DN, Rigas B, Li E
Citation(s) 26121046
Submission date Apr 07, 2015
Last update date May 15, 2019
Contact name Ellen Li
Organization name Stony Brook University
Street address Health Sciences Tower Level 17-080
City Stony Brook
State/province NY
ZIP/Postal code 11794
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (12)
GSM1652460 M8_2_APC
GSM1652461 M10_2_APC
GSM1652462 M18_2b_APC
BioProject PRJNA280522
SRA SRP056926

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Supplementary file Size Download File type/resource
GSE67634_RAW.tar 4.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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