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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

Comparison of gene profiles in hOFs and hDFs by functional annotation clustering (FAC) and pathway analysis. (a) The positional signatures of hOFs and hDFs as an internal validation. Gene expression of cranial neural crest markers for hOFs (left). Gene expression of anterior-posterior (A-P) axis markers in the body for hDFs (right). Numbers indicate the average signal values in hOFs and hDFs. (b) The top 12 clusters of FAC result in hOFs compared with hDFs. Red bar: the highest enriched cluster in hOFs > hDFs; blue bar: the highest enriched cluster in hOFs < hDFs. (c) The top 12 clusters of FAC result in the individual components of glycoproteins and transcriptional regulation in (b). (d) and (e) Pathway analysis results in genes with high (d) and low (e) expression in hOFs compared with hDFs. Indicated numbers in (b) to (e) represent enrichment scores by DAVID. The number in (d) indicates the three groups categorized in the text. The full names of each gene listed in (d) and (e) are shown in Supplementary Tables S2 and S3, respectively.
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fig3: Comparison of gene profiles in hOFs and hDFs by functional annotation clustering (FAC) and pathway analysis. (a) The positional signatures of hOFs and hDFs as an internal validation. Gene expression of cranial neural crest markers for hOFs (left). Gene expression of anterior-posterior (A-P) axis markers in the body for hDFs (right). Numbers indicate the average signal values in hOFs and hDFs. (b) The top 12 clusters of FAC result in hOFs compared with hDFs. Red bar: the highest enriched cluster in hOFs > hDFs; blue bar: the highest enriched cluster in hOFs < hDFs. (c) The top 12 clusters of FAC result in the individual components of glycoproteins and transcriptional regulation in (b). (d) and (e) Pathway analysis results in genes with high (d) and low (e) expression in hOFs compared with hDFs. Indicated numbers in (b) to (e) represent enrichment scores by DAVID. The number in (d) indicates the three groups categorized in the text. The full names of each gene listed in (d) and (e) are shown in Supplementary Tables S2 and S3, respectively.

Mentions: Since some of the expressed genes in both hOFs and hDFs must be shared in the biological pathways to display “fibroblastic” characteristics compared with those expressed in hOF-iPSCs, we next tried to elucidate the specificity between hOFs and hDFs. For this purpose, we analyzed a number of genes that were differentially expressed between hOFs and hDFs using microarray analysis, for which overlapping probes were designed and arranged within the same gene to obtain accurate results. Compared with hDFs, 232 genes were overexpressed in hOFs “hOFs > hDFs,” whereas 152 genes were underexpressed “hOFs < hDFs.” Cranial neural crest markers especially, such as distal-less homeobox 5 (DLX5), LIM homeobox 8 (LHX8), paired box 3 (PAX3), PAX9, and transcription factor AP-2 alpha (TFAP2A), were expressed at a remarkably high level in hOFs (Figure 3(a), left). On the other hand, hDFs expressed homeobox (HOX) cluster genes (Figure 3(a), right) to preserve their positional information as expected [22].


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)

Comparison of gene profiles in hOFs and hDFs by functional annotation clustering (FAC) and pathway analysis. (a) The positional signatures of hOFs and hDFs as an internal validation. Gene expression of cranial neural crest markers for hOFs (left). Gene expression of anterior-posterior (A-P) axis markers in the body for hDFs (right). Numbers indicate the average signal values in hOFs and hDFs. (b) The top 12 clusters of FAC result in hOFs compared with hDFs. Red bar: the highest enriched cluster in hOFs > hDFs; blue bar: the highest enriched cluster in hOFs < hDFs. (c) The top 12 clusters of FAC result in the individual components of glycoproteins and transcriptional regulation in (b). (d) and (e) Pathway analysis results in genes with high (d) and low (e) expression in hOFs compared with hDFs. Indicated numbers in (b) to (e) represent enrichment scores by DAVID. The number in (d) indicates the three groups categorized in the text. The full names of each gene listed in (d) and (e) are shown in Supplementary Tables S2 and S3, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4538314&req=5

fig3: Comparison of gene profiles in hOFs and hDFs by functional annotation clustering (FAC) and pathway analysis. (a) The positional signatures of hOFs and hDFs as an internal validation. Gene expression of cranial neural crest markers for hOFs (left). Gene expression of anterior-posterior (A-P) axis markers in the body for hDFs (right). Numbers indicate the average signal values in hOFs and hDFs. (b) The top 12 clusters of FAC result in hOFs compared with hDFs. Red bar: the highest enriched cluster in hOFs > hDFs; blue bar: the highest enriched cluster in hOFs < hDFs. (c) The top 12 clusters of FAC result in the individual components of glycoproteins and transcriptional regulation in (b). (d) and (e) Pathway analysis results in genes with high (d) and low (e) expression in hOFs compared with hDFs. Indicated numbers in (b) to (e) represent enrichment scores by DAVID. The number in (d) indicates the three groups categorized in the text. The full names of each gene listed in (d) and (e) are shown in Supplementary Tables S2 and S3, respectively.
Mentions: Since some of the expressed genes in both hOFs and hDFs must be shared in the biological pathways to display “fibroblastic” characteristics compared with those expressed in hOF-iPSCs, we next tried to elucidate the specificity between hOFs and hDFs. For this purpose, we analyzed a number of genes that were differentially expressed between hOFs and hDFs using microarray analysis, for which overlapping probes were designed and arranged within the same gene to obtain accurate results. Compared with hDFs, 232 genes were overexpressed in hOFs “hOFs > hDFs,” whereas 152 genes were underexpressed “hOFs < hDFs.” Cranial neural crest markers especially, such as distal-less homeobox 5 (DLX5), LIM homeobox 8 (LHX8), paired box 3 (PAX3), PAX9, and transcription factor AP-2 alpha (TFAP2A), were expressed at a remarkably high level in hOFs (Figure 3(a), left). On the other hand, hDFs expressed homeobox (HOX) cluster genes (Figure 3(a), right) to preserve their positional information as expected [22].

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