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A gene expression atlas of the domestic pig.

Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW, Dorward D, Downing A, Fairbairn L, Kapetanovic R, Raza S, Tomoiu A, Alberio R, Wu C, Su AI, Summers KM, Tuggle CK, Archibald AL, Hume DA - BMC Biol. (2012)

Bottom Line: The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed.In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human.As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, EH25 9PS, UK. tom.freeman@roslin.ed.ac.uk

ABSTRACT

Background: This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering.

Results: The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development.

Conclusions: As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites http://biogps.org and http://www.macrophages.com/pig-atlas.

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GI tract transcription factor network. A plot of the relationships inexpression among the complement of transcription factors (TFs) expressed in theporcine GI tract. TFs with similar expression profiles group together andgroupings likely represent regulatory units that work together to control cellulardifferentiation within regions of the organ. A number of TFs have been selectedthat are expressed in a very region-specific manner but whose known biology hasnot previously been associated with a functional role within this organ. GI,gastrointestinal.
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Figure 6: GI tract transcription factor network. A plot of the relationships inexpression among the complement of transcription factors (TFs) expressed in theporcine GI tract. TFs with similar expression profiles group together andgroupings likely represent regulatory units that work together to control cellulardifferentiation within regions of the organ. A number of TFs have been selectedthat are expressed in a very region-specific manner but whose known biology hasnot previously been associated with a functional role within this organ. GI,gastrointestinal.

Mentions: In our previous analysis of a mouse cell atlas, specific clusters frequently containedthe transcription factors that regulated them, and their promoters were over-representedwith the motifs that are the targets of those factors [32]. We analyzed a set of candidate transcription factors (TFs) encoded by thehuman genome [51] as a correlation network (r >0.8, MCL2.2 Figure 6). Clusters of TFs that had a preference in their expression for one ormultiple regions of the GI tract grouped together. The expression patterns of numerousother TFs imply previously unrecognized roles in regulating cell differentiation in thisorgan. RFX6 is classically associated with regulating insulin expression and hasrecently been shown to be essential for islet cell differentiation in the murinepancreas [52,53]. In the pig GI tract, the RFX6 gene was highly expressed in thesalivary gland, with significant expression in the duodenum (Figure 6b). We suggest that the RFX6 protein could also contribute toepithelial/endocrine differentiation in these organs. This suggestion is supported byprotein expression data [54], and the discovery that mutations in this gene in human Mitchell-Rileysyndrome are associated with duodenal and jejunal atresia [52]. The ONECUT2 protein is a member of a small TF family that contains a cutdomain and an atypical homeodomain. ONECUT2 has been associated with the regulation ofretinal development [55] and pancreatic and enteric endocrine differentiation [56]. In the pig gut, the gene was highly and specifically expressed in theduodenum (Figure 6c) and was tightly coexpressed with the TFPDX1 (Pancreatic and duodenal homeobox 1), a gene which is expressed byduodenal enterocytes [54], suggesting a role in defining epithelial differentiation in the region ofthe intestine. Finally, SATB2 is a homeobox protein with known roles in osteoblast [57,58] and neuronal [59,60] differentiation. The recently characterized HSA2q33.1 microdeletion syndromeis associated with genomic deletion of all or part of the human SATB2 gene [61]. In the pig, expression of this gene was exclusively found in the lowerbowel, consistent with human protein expression data [54] and its utility as a marker of colorectal derived cancers [62]. This specific expression in the epithelium of the large intestine wouldpredict a defining role in this region.


A gene expression atlas of the domestic pig.

Freeman TC, Ivens A, Baillie JK, Beraldi D, Barnett MW, Dorward D, Downing A, Fairbairn L, Kapetanovic R, Raza S, Tomoiu A, Alberio R, Wu C, Su AI, Summers KM, Tuggle CK, Archibald AL, Hume DA - BMC Biol. (2012)

GI tract transcription factor network. A plot of the relationships inexpression among the complement of transcription factors (TFs) expressed in theporcine GI tract. TFs with similar expression profiles group together andgroupings likely represent regulatory units that work together to control cellulardifferentiation within regions of the organ. A number of TFs have been selectedthat are expressed in a very region-specific manner but whose known biology hasnot previously been associated with a functional role within this organ. GI,gastrointestinal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814290&req=5

Figure 6: GI tract transcription factor network. A plot of the relationships inexpression among the complement of transcription factors (TFs) expressed in theporcine GI tract. TFs with similar expression profiles group together andgroupings likely represent regulatory units that work together to control cellulardifferentiation within regions of the organ. A number of TFs have been selectedthat are expressed in a very region-specific manner but whose known biology hasnot previously been associated with a functional role within this organ. GI,gastrointestinal.
Mentions: In our previous analysis of a mouse cell atlas, specific clusters frequently containedthe transcription factors that regulated them, and their promoters were over-representedwith the motifs that are the targets of those factors [32]. We analyzed a set of candidate transcription factors (TFs) encoded by thehuman genome [51] as a correlation network (r >0.8, MCL2.2 Figure 6). Clusters of TFs that had a preference in their expression for one ormultiple regions of the GI tract grouped together. The expression patterns of numerousother TFs imply previously unrecognized roles in regulating cell differentiation in thisorgan. RFX6 is classically associated with regulating insulin expression and hasrecently been shown to be essential for islet cell differentiation in the murinepancreas [52,53]. In the pig GI tract, the RFX6 gene was highly expressed in thesalivary gland, with significant expression in the duodenum (Figure 6b). We suggest that the RFX6 protein could also contribute toepithelial/endocrine differentiation in these organs. This suggestion is supported byprotein expression data [54], and the discovery that mutations in this gene in human Mitchell-Rileysyndrome are associated with duodenal and jejunal atresia [52]. The ONECUT2 protein is a member of a small TF family that contains a cutdomain and an atypical homeodomain. ONECUT2 has been associated with the regulation ofretinal development [55] and pancreatic and enteric endocrine differentiation [56]. In the pig gut, the gene was highly and specifically expressed in theduodenum (Figure 6c) and was tightly coexpressed with the TFPDX1 (Pancreatic and duodenal homeobox 1), a gene which is expressed byduodenal enterocytes [54], suggesting a role in defining epithelial differentiation in the region ofthe intestine. Finally, SATB2 is a homeobox protein with known roles in osteoblast [57,58] and neuronal [59,60] differentiation. The recently characterized HSA2q33.1 microdeletion syndromeis associated with genomic deletion of all or part of the human SATB2 gene [61]. In the pig, expression of this gene was exclusively found in the lowerbowel, consistent with human protein expression data [54] and its utility as a marker of colorectal derived cancers [62]. This specific expression in the epithelium of the large intestine wouldpredict a defining role in this region.

Bottom Line: The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed.In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human.As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, EH25 9PS, UK. tom.freeman@roslin.ed.ac.uk

ABSTRACT

Background: This work describes the first genome-wide analysis of the transcriptional landscape of the pig. A new porcine Affymetrix expression array was designed in order to provide comprehensive coverage of the known pig transcriptome. The new array was used to generate a genome-wide expression atlas of pig tissues derived from 62 tissue/cell types. These data were subjected to network correlation analysis and clustering.

Results: The analysis presented here provides a detailed functional clustering of the pig transcriptome where transcripts are grouped according to their expression pattern, so one can infer the function of an uncharacterized gene from the company it keeps and the locations in which it is expressed. We describe the overall transcriptional signatures present in the tissue atlas, where possible assigning those signatures to specific cell populations or pathways. In particular, we discuss the expression signatures associated with the gastrointestinal tract, an organ that was sampled at 15 sites along its length and whose biology in the pig is similar to human. We identify sets of genes that define specialized cellular compartments and region-specific digestive functions. Finally, we performed a network analysis of the transcription factors expressed in the gastrointestinal tract and demonstrate how they sub-divide into functional groups that may control cellular gastrointestinal development.

Conclusions: As an important livestock animal with a physiology that is more similar than mouse to man, we provide a major new resource for understanding gene expression with respect to the known physiology of mammalian tissues and cells. The data and analyses are available on the websites http://biogps.org and http://www.macrophages.com/pig-atlas.

Show MeSH
Related in: MedlinePlus