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Identification of novel genes selectively expressed in the follicle-associated epithelium from the meta-analysis of transcriptomics data from multiple mouse cell and tissue populations.

Kobayashi A, Donaldson DS, Kanaya T, Fukuda S, Baillie JK, Freeman TC, Ohno H, Williams IR, Mabbott NA - DNA Res. (2012)

Bottom Line: The follicle-associated epithelium (FAE) overlying the Peyer's patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium.This study provides new insight into the FAE transcriptome.Further characterization of the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.

ABSTRACT
The follicle-associated epithelium (FAE) overlying the Peyer's patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium. Using a meta-analysis approach, we identified a transcriptional signature that distinguished the FAE from a large collection of mouse cells and tissues. A co-expressed cluster of 21 FAE-specific genes was identified, and the analysis of the transcription factor binding site motifs in their promoter regions indicated that these genes shared an underlying transcriptional programme. This cluster contained known FAE- (Anxa10, Ccl20, Psg18 and Ubd) and M-cell-specific (Gp2) genes, suggesting that the others were novel FAE-specific genes. Some of these novel candidate genes were expressed highly by the FAE and M cells (Calcb, Ces3b, Clca2 and Gjb2), and others only by the FAE (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). We also identified a subset of novel FAE-related genes that were induced in the intestinal epithelium after receptor activator of nuclear factor (NF)-κB ligand stimulation. These included Mfge8 which was specific to FAE enterocytes. This study provides new insight into the FAE transcriptome. Further characterization of the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE.

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Clustering of samples based on their global gene expression profile. A Pearson correlation matrix was prepared by comparing data derived from all 130 samples used in this study performed on the Affymetrix mouse genome MOE430 2.0 expression array. A graph was constructed using sample-to-sample relationships greater than r ≥ 0.84. Nodes represent samples (individual chips) and edges are coloured according to the strength of the correlation (red, r = 1.0; blue, r ≥ 0.84). Full descriptions of the sources of each data set are given in Supplementary Table S1.
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DSS022F1: Clustering of samples based on their global gene expression profile. A Pearson correlation matrix was prepared by comparing data derived from all 130 samples used in this study performed on the Affymetrix mouse genome MOE430 2.0 expression array. A graph was constructed using sample-to-sample relationships greater than r ≥ 0.84. Nodes represent samples (individual chips) and edges are coloured according to the strength of the correlation (red, r = 1.0; blue, r ≥ 0.84). Full descriptions of the sources of each data set are given in Supplementary Table S1.

Mentions: A total of 130 gene expression data sets generated on a single microarray platform (Affymetrix MOE430-2.0) were collected representing 60 different primary mouse cells, tissues and cell lines (Supplementary Table S1). To examine the relationships between samples, a Pearson correlation matrix was first calculated based on the global expression similarities between these normalized data. The matrix was then imported into Biolayout Express3D8,9 and a graph created of the sample-to-sample correlations using the Pearson correlation relationships r ≥ 0.84 to define edges (Fig. 1). Irrespective of the source of these data sets, the different populations of intestinal, lymphoid, myeloid and mesenchymal cells clustered together and occupied specific regions of the graph. For example, most cells and tissues of intestinal origin clustered together in a distinct region of the graph (clusters 4, 5 and 10; Fig. 1). Similarly, most of the haematopoietic and lymphoid cells (clusters 2 and 13), phagocytes (cluster 3) and cells of mesenchymal origin (cluster 1) clustered together in separate regions of the graph. The CT-stimulated villous epithelium data sets were located within a different cluster from the Peyer's patch M cell and FAE data sets (clusters 5 and 4, respectively) implying distinct expression profiles.Figure 1.


Identification of novel genes selectively expressed in the follicle-associated epithelium from the meta-analysis of transcriptomics data from multiple mouse cell and tissue populations.

Kobayashi A, Donaldson DS, Kanaya T, Fukuda S, Baillie JK, Freeman TC, Ohno H, Williams IR, Mabbott NA - DNA Res. (2012)

Clustering of samples based on their global gene expression profile. A Pearson correlation matrix was prepared by comparing data derived from all 130 samples used in this study performed on the Affymetrix mouse genome MOE430 2.0 expression array. A graph was constructed using sample-to-sample relationships greater than r ≥ 0.84. Nodes represent samples (individual chips) and edges are coloured according to the strength of the correlation (red, r = 1.0; blue, r ≥ 0.84). Full descriptions of the sources of each data set are given in Supplementary Table S1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3473373&req=5

DSS022F1: Clustering of samples based on their global gene expression profile. A Pearson correlation matrix was prepared by comparing data derived from all 130 samples used in this study performed on the Affymetrix mouse genome MOE430 2.0 expression array. A graph was constructed using sample-to-sample relationships greater than r ≥ 0.84. Nodes represent samples (individual chips) and edges are coloured according to the strength of the correlation (red, r = 1.0; blue, r ≥ 0.84). Full descriptions of the sources of each data set are given in Supplementary Table S1.
Mentions: A total of 130 gene expression data sets generated on a single microarray platform (Affymetrix MOE430-2.0) were collected representing 60 different primary mouse cells, tissues and cell lines (Supplementary Table S1). To examine the relationships between samples, a Pearson correlation matrix was first calculated based on the global expression similarities between these normalized data. The matrix was then imported into Biolayout Express3D8,9 and a graph created of the sample-to-sample correlations using the Pearson correlation relationships r ≥ 0.84 to define edges (Fig. 1). Irrespective of the source of these data sets, the different populations of intestinal, lymphoid, myeloid and mesenchymal cells clustered together and occupied specific regions of the graph. For example, most cells and tissues of intestinal origin clustered together in a distinct region of the graph (clusters 4, 5 and 10; Fig. 1). Similarly, most of the haematopoietic and lymphoid cells (clusters 2 and 13), phagocytes (cluster 3) and cells of mesenchymal origin (cluster 1) clustered together in separate regions of the graph. The CT-stimulated villous epithelium data sets were located within a different cluster from the Peyer's patch M cell and FAE data sets (clusters 5 and 4, respectively) implying distinct expression profiles.Figure 1.

Bottom Line: The follicle-associated epithelium (FAE) overlying the Peyer's patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium.This study provides new insight into the FAE transcriptome.Further characterization of the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE.

View Article: PubMed Central - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.

ABSTRACT
The follicle-associated epithelium (FAE) overlying the Peyer's patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium. Using a meta-analysis approach, we identified a transcriptional signature that distinguished the FAE from a large collection of mouse cells and tissues. A co-expressed cluster of 21 FAE-specific genes was identified, and the analysis of the transcription factor binding site motifs in their promoter regions indicated that these genes shared an underlying transcriptional programme. This cluster contained known FAE- (Anxa10, Ccl20, Psg18 and Ubd) and M-cell-specific (Gp2) genes, suggesting that the others were novel FAE-specific genes. Some of these novel candidate genes were expressed highly by the FAE and M cells (Calcb, Ces3b, Clca2 and Gjb2), and others only by the FAE (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). We also identified a subset of novel FAE-related genes that were induced in the intestinal epithelium after receptor activator of nuclear factor (NF)-κB ligand stimulation. These included Mfge8 which was specific to FAE enterocytes. This study provides new insight into the FAE transcriptome. Further characterization of the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE.

Show MeSH