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Gene Signature of Human Oral Mucosa Fibroblasts: Comparison with Dermal Fibroblasts and Induced Pluripotent Stem Cells.

Miyoshi K, Horiguchi T, Tanimura A, Hagita H, Noma T - Biomed Res Int (2015)

Bottom Line: As a common feature of fibroblasts, both hOFs and hDFs expressed glycolipid metabolism-related genes at higher levels compared with hOF-iPSCs.Distinct characteristics of hOFs compared with hDFs included a high expression of glycoprotein genes, involved in signaling, extracellular matrix, membrane, and receptor proteins, besides a low expression of HOX genes, the hDFs-markers.The results of the pathway analyses indicated that tissue-reconstructive, proliferative, and signaling pathways are active, whereas senescence-related genes in p53 pathway are inactive in hOFs.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.

ABSTRACT
Oral mucosa is a useful material for regeneration therapy with the advantages of its accessibility and versatility regardless of age and gender. However, little is known about the molecular characteristics of oral mucosa. Here we report the first comparative profiles of the gene signatures of human oral mucosa fibroblasts (hOFs), human dermal fibroblasts (hDFs), and hOF-derived induced pluripotent stem cells (hOF-iPSCs), linking these with biological roles by functional annotation and pathway analyses. As a common feature of fibroblasts, both hOFs and hDFs expressed glycolipid metabolism-related genes at higher levels compared with hOF-iPSCs. Distinct characteristics of hOFs compared with hDFs included a high expression of glycoprotein genes, involved in signaling, extracellular matrix, membrane, and receptor proteins, besides a low expression of HOX genes, the hDFs-markers. The results of the pathway analyses indicated that tissue-reconstructive, proliferative, and signaling pathways are active, whereas senescence-related genes in p53 pathway are inactive in hOFs. Furthermore, more than half of hOF-specific genes were similarly expressed to those of hOF-iPSC genes and might be controlled by WNT signaling. Our findings demonstrated that hOFs have unique cellular characteristics in specificity and plasticity. These data may provide useful insight into application of oral fibroblasts for direct reprograming.

No MeSH data available.


Related in: MedlinePlus

Gene expression signatures in hOFs, hDFs, and hOF-iPSCs. (a) Heat map and hierarchical clustering of whole microarray probes for each of the nine samples. Three individual samples were prepared from each of three types of cells, hOFs, hDFs, and hOF-iPSCs. (b) Comparisons of average signal values among the three types of cells, hOFs, hDFs, and hOF-iPSCs. The number indicates differentially expressed genes (p < 0.05, ≥2-fold change; upper panel, left). Scatter plots comparing the average signal values of three samples are shown and the number of differentially expressed probes at more than 2-fold levels is indicated as follows: hOFs versus hDFs (upper panel, right), hOFs versus hOF-iPSCs (lower panel, left), and hDFs versus hOF-iPSCs (lower panel, right).
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fig1: Gene expression signatures in hOFs, hDFs, and hOF-iPSCs. (a) Heat map and hierarchical clustering of whole microarray probes for each of the nine samples. Three individual samples were prepared from each of three types of cells, hOFs, hDFs, and hOF-iPSCs. (b) Comparisons of average signal values among the three types of cells, hOFs, hDFs, and hOF-iPSCs. The number indicates differentially expressed genes (p < 0.05, ≥2-fold change; upper panel, left). Scatter plots comparing the average signal values of three samples are shown and the number of differentially expressed probes at more than 2-fold levels is indicated as follows: hOFs versus hDFs (upper panel, right), hOFs versus hOF-iPSCs (lower panel, left), and hDFs versus hOF-iPSCs (lower panel, right).

Mentions: To analyze the molecular profile of hOFs, we prepared three types of cells, hOFs, hDFs, and hOF-iPSCs. Three independent cell lines from different donors were chosen to obtain accurate results from each cell type. Heat map and hierarchical clustering analysis revealed that the gene expression pattern in each group was conserved, except for hDF3 (TIG114) and hOF4, for which intermediate patterns between fibroblasts and hOF-iPSCs were identified (Figure 1(a)). Notably, 56% of probes were expressed at the similar levels (16,156 out of 28,869 probes; less than 2-fold difference) among hOFs, hDFs, and OF-iPSCs. While our samples were not exact age- and gender-matched samples, we observed the strong correlation among the samples by Pearson's correlation coefficient analysis (Supplementary Figure S1A). Each correlation coefficient value among the samples in each group, and also that between hOFs and hDFs, was within the range between 0.9 and 1.0. Furthermore, each correlation coefficient value between either hOFs or hDFs and hOF-iPSCs was within the range between 0.7 and 0.8. These results indicated that our data may, at least in part, exclude the issues about age and gender difference with the strong correlation among the samples. The reliability of microarray hybridization techniques were confirmed by the company-supplied hybrydization control (Figure S1B).


Gene Signature of Human Oral Mucosa Fibroblasts: Comparison with Dermal Fibroblasts and Induced Pluripotent Stem Cells.

Miyoshi K, Horiguchi T, Tanimura A, Hagita H, Noma T - Biomed Res Int (2015)

Gene expression signatures in hOFs, hDFs, and hOF-iPSCs. (a) Heat map and hierarchical clustering of whole microarray probes for each of the nine samples. Three individual samples were prepared from each of three types of cells, hOFs, hDFs, and hOF-iPSCs. (b) Comparisons of average signal values among the three types of cells, hOFs, hDFs, and hOF-iPSCs. The number indicates differentially expressed genes (p < 0.05, ≥2-fold change; upper panel, left). Scatter plots comparing the average signal values of three samples are shown and the number of differentially expressed probes at more than 2-fold levels is indicated as follows: hOFs versus hDFs (upper panel, right), hOFs versus hOF-iPSCs (lower panel, left), and hDFs versus hOF-iPSCs (lower panel, right).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4538314&req=5

fig1: Gene expression signatures in hOFs, hDFs, and hOF-iPSCs. (a) Heat map and hierarchical clustering of whole microarray probes for each of the nine samples. Three individual samples were prepared from each of three types of cells, hOFs, hDFs, and hOF-iPSCs. (b) Comparisons of average signal values among the three types of cells, hOFs, hDFs, and hOF-iPSCs. The number indicates differentially expressed genes (p < 0.05, ≥2-fold change; upper panel, left). Scatter plots comparing the average signal values of three samples are shown and the number of differentially expressed probes at more than 2-fold levels is indicated as follows: hOFs versus hDFs (upper panel, right), hOFs versus hOF-iPSCs (lower panel, left), and hDFs versus hOF-iPSCs (lower panel, right).
Mentions: To analyze the molecular profile of hOFs, we prepared three types of cells, hOFs, hDFs, and hOF-iPSCs. Three independent cell lines from different donors were chosen to obtain accurate results from each cell type. Heat map and hierarchical clustering analysis revealed that the gene expression pattern in each group was conserved, except for hDF3 (TIG114) and hOF4, for which intermediate patterns between fibroblasts and hOF-iPSCs were identified (Figure 1(a)). Notably, 56% of probes were expressed at the similar levels (16,156 out of 28,869 probes; less than 2-fold difference) among hOFs, hDFs, and OF-iPSCs. While our samples were not exact age- and gender-matched samples, we observed the strong correlation among the samples by Pearson's correlation coefficient analysis (Supplementary Figure S1A). Each correlation coefficient value among the samples in each group, and also that between hOFs and hDFs, was within the range between 0.9 and 1.0. Furthermore, each correlation coefficient value between either hOFs or hDFs and hOF-iPSCs was within the range between 0.7 and 0.8. These results indicated that our data may, at least in part, exclude the issues about age and gender difference with the strong correlation among the samples. The reliability of microarray hybridization techniques were confirmed by the company-supplied hybrydization control (Figure S1B).

Bottom Line: As a common feature of fibroblasts, both hOFs and hDFs expressed glycolipid metabolism-related genes at higher levels compared with hOF-iPSCs.Distinct characteristics of hOFs compared with hDFs included a high expression of glycoprotein genes, involved in signaling, extracellular matrix, membrane, and receptor proteins, besides a low expression of HOX genes, the hDFs-markers.The results of the pathway analyses indicated that tissue-reconstructive, proliferative, and signaling pathways are active, whereas senescence-related genes in p53 pathway are inactive in hOFs.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.

ABSTRACT
Oral mucosa is a useful material for regeneration therapy with the advantages of its accessibility and versatility regardless of age and gender. However, little is known about the molecular characteristics of oral mucosa. Here we report the first comparative profiles of the gene signatures of human oral mucosa fibroblasts (hOFs), human dermal fibroblasts (hDFs), and hOF-derived induced pluripotent stem cells (hOF-iPSCs), linking these with biological roles by functional annotation and pathway analyses. As a common feature of fibroblasts, both hOFs and hDFs expressed glycolipid metabolism-related genes at higher levels compared with hOF-iPSCs. Distinct characteristics of hOFs compared with hDFs included a high expression of glycoprotein genes, involved in signaling, extracellular matrix, membrane, and receptor proteins, besides a low expression of HOX genes, the hDFs-markers. The results of the pathway analyses indicated that tissue-reconstructive, proliferative, and signaling pathways are active, whereas senescence-related genes in p53 pathway are inactive in hOFs. Furthermore, more than half of hOF-specific genes were similarly expressed to those of hOF-iPSC genes and might be controlled by WNT signaling. Our findings demonstrated that hOFs have unique cellular characteristics in specificity and plasticity. These data may provide useful insight into application of oral fibroblasts for direct reprograming.

No MeSH data available.


Related in: MedlinePlus