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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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Network analysis of mouse cell and tissue transcriptomics data. (A) Main component of the network graph derived from 130 samples of mouse cell and tissue populations run on Affymetrix MOE430_2 arrays. Nodes represent transcripts (probe sets) and the edges represent correlations between individual expression profiles above r ≥ 0.85. The boxed area (right) shows three representative clusters derived from the network graph and their mean probe set expression profile across all data sets. BM prog., bone marrow progenitor cells; DC, dendritic cell; pDC, plasmacytoid DC; FDC, follicular dendritic cell; Endo., endothelium; LTi, lymphoid tissue-inducer cells; NH, natural helper. (B) Shadow image of the network graph (edges only indicated by grey lines) with the boundaries of distinct transcriptional networks with related function indicated. Cluster 65 (FAE and Peyer's patch M cell-related) is highlighted.
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DSS022F2: Network analysis of mouse cell and tissue transcriptomics data. (A) Main component of the network graph derived from 130 samples of mouse cell and tissue populations run on Affymetrix MOE430_2 arrays. Nodes represent transcripts (probe sets) and the edges represent correlations between individual expression profiles above r ≥ 0.85. The boxed area (right) shows three representative clusters derived from the network graph and their mean probe set expression profile across all data sets. BM prog., bone marrow progenitor cells; DC, dendritic cell; pDC, plasmacytoid DC; FDC, follicular dendritic cell; Endo., endothelium; LTi, lymphoid tissue-inducer cells; NH, natural helper. (B) Shadow image of the network graph (edges only indicated by grey lines) with the boundaries of distinct transcriptional networks with related function indicated. Cluster 65 (FAE and Peyer's patch M cell-related) is highlighted.

Mentions: The network graph's topology is derived from cliques of genes which are co-expressed (Fig. 2). Clusters containing genes with related expression patterns were typically localized within similar neighbourhoods of the network graph (Fig. 2B). For example, clusters 2, 17, 36 and 49 were highly expressed by all the intestine-derived data sets and occupied the same region of the network graph, adjacent to the other intestine-related clusters (Fig. 2). Clusters 3, 25 and 40 were highly expressed by Paneth cells and occupied a distinct region of the graph distant from the other intestine-related clusters, but adjacent to the rest of the Paneth cell-related clusters (Fig. 2). Other clusters, such as those expressed highly by B cells (cluster 22), mononuclear phagocytes (cluster 24) and other lymphocyte, leukocyte and haematopoietic cell lineages occupied a specific region of the graph geographically distant from the intestine-related clusters.Figure 2.


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)

Network analysis of mouse cell and tissue transcriptomics data. (A) Main component of the network graph derived from 130 samples of mouse cell and tissue populations run on Affymetrix MOE430_2 arrays. Nodes represent transcripts (probe sets) and the edges represent correlations between individual expression profiles above r ≥ 0.85. The boxed area (right) shows three representative clusters derived from the network graph and their mean probe set expression profile across all data sets. BM prog., bone marrow progenitor cells; DC, dendritic cell; pDC, plasmacytoid DC; FDC, follicular dendritic cell; Endo., endothelium; LTi, lymphoid tissue-inducer cells; NH, natural helper. (B) Shadow image of the network graph (edges only indicated by grey lines) with the boundaries of distinct transcriptional networks with related function indicated. Cluster 65 (FAE and Peyer's patch M cell-related) is highlighted.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DSS022F2: Network analysis of mouse cell and tissue transcriptomics data. (A) Main component of the network graph derived from 130 samples of mouse cell and tissue populations run on Affymetrix MOE430_2 arrays. Nodes represent transcripts (probe sets) and the edges represent correlations between individual expression profiles above r ≥ 0.85. The boxed area (right) shows three representative clusters derived from the network graph and their mean probe set expression profile across all data sets. BM prog., bone marrow progenitor cells; DC, dendritic cell; pDC, plasmacytoid DC; FDC, follicular dendritic cell; Endo., endothelium; LTi, lymphoid tissue-inducer cells; NH, natural helper. (B) Shadow image of the network graph (edges only indicated by grey lines) with the boundaries of distinct transcriptional networks with related function indicated. Cluster 65 (FAE and Peyer's patch M cell-related) is highlighted.
Mentions: The network graph's topology is derived from cliques of genes which are co-expressed (Fig. 2). Clusters containing genes with related expression patterns were typically localized within similar neighbourhoods of the network graph (Fig. 2B). For example, clusters 2, 17, 36 and 49 were highly expressed by all the intestine-derived data sets and occupied the same region of the network graph, adjacent to the other intestine-related clusters (Fig. 2). Clusters 3, 25 and 40 were highly expressed by Paneth cells and occupied a distinct region of the graph distant from the other intestine-related clusters, but adjacent to the rest of the Paneth cell-related clusters (Fig. 2). Other clusters, such as those expressed highly by B cells (cluster 22), mononuclear phagocytes (cluster 24) and other lymphocyte, leukocyte and haematopoietic cell lineages occupied a specific region of the graph geographically distant from the intestine-related clusters.Figure 2.

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
Related in: MedlinePlus