Limits...
Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.

Higuchi Y, Kojima M, Ishii G, Aoyagi K, Sasaki H, Ochiai A - PLoS ONE (2015)

Bottom Line: The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered.These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.

ABSTRACT

Background: Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.

Methods: Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs) were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs) and the subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.

Results: In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.

Conclusions: GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

No MeSH data available.


The Transcriptional Differences between Gastrointestinal Fibroblasts and Non–Gastrointestinal Fibroblasts.(A) Supervised clustering using the significant different expressed probe sets between gastrointestinal fibroblasts (GIFs) and non-GIFs. The 995 significant probe sets were selected based on P < 0.05 and fold change > 2.0 (one-way ANOVA). The red bars indicate a GIF sample, and blue bars indicate a non-GIF sample. The top significant genes are shown on the right. The color scale of gene expression is the same as Fig 1A. (B) Distinct expression of the genes related with transcriptional regulation, signal ligands, and extracellular matrix remodeling in GIFs and Non-GIFs.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4457624&req=5

pone.0129241.g002: The Transcriptional Differences between Gastrointestinal Fibroblasts and Non–Gastrointestinal Fibroblasts.(A) Supervised clustering using the significant different expressed probe sets between gastrointestinal fibroblasts (GIFs) and non-GIFs. The 995 significant probe sets were selected based on P < 0.05 and fold change > 2.0 (one-way ANOVA). The red bars indicate a GIF sample, and blue bars indicate a non-GIF sample. The top significant genes are shown on the right. The color scale of gene expression is the same as Fig 1A. (B) Distinct expression of the genes related with transcriptional regulation, signal ligands, and extracellular matrix remodeling in GIFs and Non-GIFs.

Mentions: Next, we selected the significant different expressing probe sets between GIFs and non-GIFs, and a supervised hierarchical clustering analysis was performed. We selected 995 probe sets of GIF signature genes based on P < 0.05 (unpaired t-test) and fold change > 2.0 (Fig 2A and S4 Table). The GIF signature genes consisted of many genes related with transcriptional regulation (transcriptional factors and co-factors), signal ligands (growth factors, cytokine, chemokine and other hormonal factors), and extracellular matrix regeneration (collagen molecules, proteoglycans, matrix metalloproteinase: Fig 2B). In addition, the validation study of these signature genes was performed using 8 independent microarray data sets of human primary fibroblasts in public GEO datasets, including 3 sets of colon mucosal fibroblasts (GSE15322, GSE29316, GSE39394), 1 set of stomach mucosal fibroblasts (GSE44740), 2 sets of normal mammary gland fibroblasts (GSE20086, GSE25619), and 2 sets of lung fibroblasts (GSE23066, GSE44723; lung tissue and airway fibroblasts). By hierarchical cluster analysis using 995 GIF signature genes, we successfully determined that the first bifurcation of the dendrogram separated 11 GIF samples and 18 non-GIF samples into different clusters (S2A–S2C Fig). These results revealed that the differences between GIFs and non–GIFs were characterized by their expression of genes related to transcriptional regulation, signal ligands, and extracellular matrix remodeling.


Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.

Higuchi Y, Kojima M, Ishii G, Aoyagi K, Sasaki H, Ochiai A - PLoS ONE (2015)

The Transcriptional Differences between Gastrointestinal Fibroblasts and Non–Gastrointestinal Fibroblasts.(A) Supervised clustering using the significant different expressed probe sets between gastrointestinal fibroblasts (GIFs) and non-GIFs. The 995 significant probe sets were selected based on P < 0.05 and fold change > 2.0 (one-way ANOVA). The red bars indicate a GIF sample, and blue bars indicate a non-GIF sample. The top significant genes are shown on the right. The color scale of gene expression is the same as Fig 1A. (B) Distinct expression of the genes related with transcriptional regulation, signal ligands, and extracellular matrix remodeling in GIFs and Non-GIFs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4457624&req=5

pone.0129241.g002: The Transcriptional Differences between Gastrointestinal Fibroblasts and Non–Gastrointestinal Fibroblasts.(A) Supervised clustering using the significant different expressed probe sets between gastrointestinal fibroblasts (GIFs) and non-GIFs. The 995 significant probe sets were selected based on P < 0.05 and fold change > 2.0 (one-way ANOVA). The red bars indicate a GIF sample, and blue bars indicate a non-GIF sample. The top significant genes are shown on the right. The color scale of gene expression is the same as Fig 1A. (B) Distinct expression of the genes related with transcriptional regulation, signal ligands, and extracellular matrix remodeling in GIFs and Non-GIFs.
Mentions: Next, we selected the significant different expressing probe sets between GIFs and non-GIFs, and a supervised hierarchical clustering analysis was performed. We selected 995 probe sets of GIF signature genes based on P < 0.05 (unpaired t-test) and fold change > 2.0 (Fig 2A and S4 Table). The GIF signature genes consisted of many genes related with transcriptional regulation (transcriptional factors and co-factors), signal ligands (growth factors, cytokine, chemokine and other hormonal factors), and extracellular matrix regeneration (collagen molecules, proteoglycans, matrix metalloproteinase: Fig 2B). In addition, the validation study of these signature genes was performed using 8 independent microarray data sets of human primary fibroblasts in public GEO datasets, including 3 sets of colon mucosal fibroblasts (GSE15322, GSE29316, GSE39394), 1 set of stomach mucosal fibroblasts (GSE44740), 2 sets of normal mammary gland fibroblasts (GSE20086, GSE25619), and 2 sets of lung fibroblasts (GSE23066, GSE44723; lung tissue and airway fibroblasts). By hierarchical cluster analysis using 995 GIF signature genes, we successfully determined that the first bifurcation of the dendrogram separated 11 GIF samples and 18 non-GIF samples into different clusters (S2A–S2C Fig). These results revealed that the differences between GIFs and non–GIFs were characterized by their expression of genes related to transcriptional regulation, signal ligands, and extracellular matrix remodeling.

Bottom Line: The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered.These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.

ABSTRACT

Background: Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.

Methods: Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs) were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs) and the subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.

Results: In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.

Conclusions: GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

No MeSH data available.