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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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The average expression profiles of the genes in selected clusters over the 130 samples. x-axis shows samples, grouped according to the cell type (in order of presentation in Supplementary Table S1). y-axis shows mean signal expression intensity for the cluster (probe set intensity). Expression profiles of: (A) extracellular matrix-related gene clusters (cluster 13, red; cluster 51, blue); (B) phagocytes (green, cluster 24), B cells (red, cluster 22) and T cells (blue, cluster 31); (C) LTi cells (red, cluster 78) and natural helper cells (green, cluster 20); (D) Paneth cells (red, cluster 3; blue, cluster 34; yellow, cluster 80); (E) house-keeping (e.g. cell cycle) genes (dark blue, cluster 19; light blue, cluster 21; green, cluster 54); (F) RNA processing genes (cluster 16).
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DSS022F3: The average expression profiles of the genes in selected clusters over the 130 samples. x-axis shows samples, grouped according to the cell type (in order of presentation in Supplementary Table S1). y-axis shows mean signal expression intensity for the cluster (probe set intensity). Expression profiles of: (A) extracellular matrix-related gene clusters (cluster 13, red; cluster 51, blue); (B) phagocytes (green, cluster 24), B cells (red, cluster 22) and T cells (blue, cluster 31); (C) LTi cells (red, cluster 78) and natural helper cells (green, cluster 20); (D) Paneth cells (red, cluster 3; blue, cluster 34; yellow, cluster 80); (E) house-keeping (e.g. cell cycle) genes (dark blue, cluster 19; light blue, cluster 21; green, cluster 54); (F) RNA processing genes (cluster 16).

Mentions: The average expression profile of the probe sets (and the genes they encode) within the individual clusters can give a strong indication of the biology they encode. Many tissue/cell-specific gene clusters were identified. The mean expression profiles of the genes in a selection of example clusters derived from the network graph are shown in Fig. 3, and the mean expression profiles of every cluster are provided in Supplementary Fig. S1. For example, cluster 13 contained many genes characteristically expressed by mesenchymal cells, especially those encoding components of the extracellular matrix (Fig. 3A). Cluster 22 contained genes characteristically expressed by B cells including those encoding immunoglobulins and the major histocompatibility complex class II complex. Cluster 31 contained genes related to T cell activity, cluster 24 was enriched with genes related to mononuclear phagocyte activity including constituents of the lysosomal proton pump (Atp6v0a1etc.; Fig. 3B). Cluster 20 was enriched with genes expressed by natural helper cells, whereas cluster 78 was enriched with genes expressed by lymphoid tissue-inducer cells (Fig. 3C). Several Paneth cell-related clusters were also identified which contained typical genes related to their activity including (Fig. 3D). Some clusters were expressed highly across all samples and predominantly contained housekeeping genes. For example, clusters 19, 21 and 54 were enriched cell cycle-related genes (Fig. 3E), whereas cluster 16 contained genes involved with RNA processing (Fig. 3F).Figure 3.


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)

The average expression profiles of the genes in selected clusters over the 130 samples. x-axis shows samples, grouped according to the cell type (in order of presentation in Supplementary Table S1). y-axis shows mean signal expression intensity for the cluster (probe set intensity). Expression profiles of: (A) extracellular matrix-related gene clusters (cluster 13, red; cluster 51, blue); (B) phagocytes (green, cluster 24), B cells (red, cluster 22) and T cells (blue, cluster 31); (C) LTi cells (red, cluster 78) and natural helper cells (green, cluster 20); (D) Paneth cells (red, cluster 3; blue, cluster 34; yellow, cluster 80); (E) house-keeping (e.g. cell cycle) genes (dark blue, cluster 19; light blue, cluster 21; green, cluster 54); (F) RNA processing genes (cluster 16).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DSS022F3: The average expression profiles of the genes in selected clusters over the 130 samples. x-axis shows samples, grouped according to the cell type (in order of presentation in Supplementary Table S1). y-axis shows mean signal expression intensity for the cluster (probe set intensity). Expression profiles of: (A) extracellular matrix-related gene clusters (cluster 13, red; cluster 51, blue); (B) phagocytes (green, cluster 24), B cells (red, cluster 22) and T cells (blue, cluster 31); (C) LTi cells (red, cluster 78) and natural helper cells (green, cluster 20); (D) Paneth cells (red, cluster 3; blue, cluster 34; yellow, cluster 80); (E) house-keeping (e.g. cell cycle) genes (dark blue, cluster 19; light blue, cluster 21; green, cluster 54); (F) RNA processing genes (cluster 16).
Mentions: The average expression profile of the probe sets (and the genes they encode) within the individual clusters can give a strong indication of the biology they encode. Many tissue/cell-specific gene clusters were identified. The mean expression profiles of the genes in a selection of example clusters derived from the network graph are shown in Fig. 3, and the mean expression profiles of every cluster are provided in Supplementary Fig. S1. For example, cluster 13 contained many genes characteristically expressed by mesenchymal cells, especially those encoding components of the extracellular matrix (Fig. 3A). Cluster 22 contained genes characteristically expressed by B cells including those encoding immunoglobulins and the major histocompatibility complex class II complex. Cluster 31 contained genes related to T cell activity, cluster 24 was enriched with genes related to mononuclear phagocyte activity including constituents of the lysosomal proton pump (Atp6v0a1etc.; Fig. 3B). Cluster 20 was enriched with genes expressed by natural helper cells, whereas cluster 78 was enriched with genes expressed by lymphoid tissue-inducer cells (Fig. 3C). Several Paneth cell-related clusters were also identified which contained typical genes related to their activity including (Fig. 3D). Some clusters were expressed highly across all samples and predominantly contained housekeeping genes. For example, clusters 19, 21 and 54 were enriched cell cycle-related genes (Fig. 3E), whereas cluster 16 contained genes involved with RNA processing (Fig. 3F).Figure 3.

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