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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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Cartoon illustrating the putative functions of the FAE- and M-cell-related genes identified in this study. Genes were classified into groupings of related cellular function based on published data from literature searches. Red font, RANKL-dependent genes; plain font, RANKL-independent genes.
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DSS022F8: Cartoon illustrating the putative functions of the FAE- and M-cell-related genes identified in this study. Genes were classified into groupings of related cellular function based on published data from literature searches. Red font, RANKL-dependent genes; plain font, RANKL-independent genes.

Mentions: Here, we used a meta-analysis approach to identify a co-expressed transcriptional signature that distinguished the FAE from a large collection of mouse primary cells, tissues and cell lines. A co-expressed gene cluster (cluster 65) was identified which was highly expressed only in the FAE and by M cells and was enriched with known M-cell- (Gp2) or FAE-specific (Anxa10, Ccl20, Psg18 and Ubd)2,4,13–15 genes. Such clusters of co-expressed genes provide an opportunity to identify novel lineage markers and regulators of cell function, as well as functions for uncharacterized genes. For example, recent studies show that the broad complex, tramtrack, bric-a-brac, and zinc finger transcription factor Zbt46 is specifically expressed by all classical DC lineages.27,28 Retrospective analysis of data from our previous comparison of the transcriptomes of different mouse lymphocyte and leukocyte populations shows that Zbtb46 was co-expressed in a cluster of 12 genes whose expression was restricted to classical DC (cluster 79 in Mabbott et al.7). By applying the principle of ‘guilt-by-association’, this suggested that the other genes co-expressed within cluster 65 in the current study were also FAE-related. These novel FAE-related genes could be separated into two groups: those expressed highly within the FAE and by M cells (Calcb, Ces3b, Clca2 and Gjb2) and those expressed in the FAE, but not by M cells (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). These genes could also be further subdivided depending on their requirement for RANKL-stimulation for their expression. The potential functions of the FAE-related genes identified in this study are summarized in Fig. 8 and examples discussed below.Figure 8.


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)

Cartoon illustrating the putative functions of the FAE- and M-cell-related genes identified in this study. Genes were classified into groupings of related cellular function based on published data from literature searches. Red font, RANKL-dependent genes; plain font, RANKL-independent genes.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DSS022F8: Cartoon illustrating the putative functions of the FAE- and M-cell-related genes identified in this study. Genes were classified into groupings of related cellular function based on published data from literature searches. Red font, RANKL-dependent genes; plain font, RANKL-independent genes.
Mentions: Here, we used a meta-analysis approach to identify a co-expressed transcriptional signature that distinguished the FAE from a large collection of mouse primary cells, tissues and cell lines. A co-expressed gene cluster (cluster 65) was identified which was highly expressed only in the FAE and by M cells and was enriched with known M-cell- (Gp2) or FAE-specific (Anxa10, Ccl20, Psg18 and Ubd)2,4,13–15 genes. Such clusters of co-expressed genes provide an opportunity to identify novel lineage markers and regulators of cell function, as well as functions for uncharacterized genes. For example, recent studies show that the broad complex, tramtrack, bric-a-brac, and zinc finger transcription factor Zbt46 is specifically expressed by all classical DC lineages.27,28 Retrospective analysis of data from our previous comparison of the transcriptomes of different mouse lymphocyte and leukocyte populations shows that Zbtb46 was co-expressed in a cluster of 12 genes whose expression was restricted to classical DC (cluster 79 in Mabbott et al.7). By applying the principle of ‘guilt-by-association’, this suggested that the other genes co-expressed within cluster 65 in the current study were also FAE-related. These novel FAE-related genes could be separated into two groups: those expressed highly within the FAE and by M cells (Calcb, Ces3b, Clca2 and Gjb2) and those expressed in the FAE, but not by M cells (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). These genes could also be further subdivided depending on their requirement for RANKL-stimulation for their expression. The potential functions of the FAE-related genes identified in this study are summarized in Fig. 8 and examples discussed below.Figure 8.

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