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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

Pathway analysis of human fibroblasts and hOF-iPSCs. (a) Gene expression of ESCs markers and reprogramming factors. The numbers indicate average signal values in each cell type. Red: highly expressed genes in hOFs and hDFs compared with hiPSCs. (b) and (c) Pathways with low (b) and high (c) expression in human fibroblasts compared with those in hOF-iPSCs. Numbers indicate enrichment scores provided by DAVID. The top three clusters are colored. Blanks indicate “not listed” in the samples. The top three clusters are highlighted in blue (b) and in red (c), respectively. (d) A diagram of various GSL-biosynthetic pathways. Red and blue colors indicate genes with high and low expressions in human fibroblasts, respectively. cer: ceramide; Gb with subscript: globoside with the number of carbohydrates; G with subscript: ganglioside with subclass; Lc with subscript: lacto- with the number of carbohydrates; nLc-: neolacto-; Fuc: fucose; GalNAc: N-acetylgalactosamine; NeuAc: N-acetylneuraminic acid. (e) Individual gene-expression levels of each GSL-biosynthetic pathway in hOFs, hDFs, and hOF-iPSCs. Red and Blue indicate the same as in (d).
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fig2: Pathway analysis of human fibroblasts and hOF-iPSCs. (a) Gene expression of ESCs markers and reprogramming factors. The numbers indicate average signal values in each cell type. Red: highly expressed genes in hOFs and hDFs compared with hiPSCs. (b) and (c) Pathways with low (b) and high (c) expression in human fibroblasts compared with those in hOF-iPSCs. Numbers indicate enrichment scores provided by DAVID. The top three clusters are colored. Blanks indicate “not listed” in the samples. The top three clusters are highlighted in blue (b) and in red (c), respectively. (d) A diagram of various GSL-biosynthetic pathways. Red and blue colors indicate genes with high and low expressions in human fibroblasts, respectively. cer: ceramide; Gb with subscript: globoside with the number of carbohydrates; G with subscript: ganglioside with subclass; Lc with subscript: lacto- with the number of carbohydrates; nLc-: neolacto-; Fuc: fucose; GalNAc: N-acetylgalactosamine; NeuAc: N-acetylneuraminic acid. (e) Individual gene-expression levels of each GSL-biosynthetic pathway in hOFs, hDFs, and hOF-iPSCs. Red and Blue indicate the same as in (d).

Mentions: At the beginning, we confirmed the expression levels of several embryonic stem cells (ESCs) markers and reprogramming factors that had been generally observed in iPSCs (Figure 2(a)). As expected, hOF-iPSCs highly expressed all pluripotent markers tested for, that is, micro RNA302a (MIR302A), MIR302B, lin-28 homolog A (LIN28A), Nanog homeobox (NANOG), developmental pluripotency associated 4 (DPPA4), glypican 4 (GPC4), prominin 1 (PROM1), growth differentiation factor 3 (GDF3), POU5F1/OCT4, and SOX2. We also found that the reprogramming factors KLF4 and c-MYC were highly expressed in hOFs and hDFs than in hOF-iPSCs. These results were consistent with previous observations [5].


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)

Pathway analysis of human fibroblasts and hOF-iPSCs. (a) Gene expression of ESCs markers and reprogramming factors. The numbers indicate average signal values in each cell type. Red: highly expressed genes in hOFs and hDFs compared with hiPSCs. (b) and (c) Pathways with low (b) and high (c) expression in human fibroblasts compared with those in hOF-iPSCs. Numbers indicate enrichment scores provided by DAVID. The top three clusters are colored. Blanks indicate “not listed” in the samples. The top three clusters are highlighted in blue (b) and in red (c), respectively. (d) A diagram of various GSL-biosynthetic pathways. Red and blue colors indicate genes with high and low expressions in human fibroblasts, respectively. cer: ceramide; Gb with subscript: globoside with the number of carbohydrates; G with subscript: ganglioside with subclass; Lc with subscript: lacto- with the number of carbohydrates; nLc-: neolacto-; Fuc: fucose; GalNAc: N-acetylgalactosamine; NeuAc: N-acetylneuraminic acid. (e) Individual gene-expression levels of each GSL-biosynthetic pathway in hOFs, hDFs, and hOF-iPSCs. Red and Blue indicate the same as in (d).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4538314&req=5

fig2: Pathway analysis of human fibroblasts and hOF-iPSCs. (a) Gene expression of ESCs markers and reprogramming factors. The numbers indicate average signal values in each cell type. Red: highly expressed genes in hOFs and hDFs compared with hiPSCs. (b) and (c) Pathways with low (b) and high (c) expression in human fibroblasts compared with those in hOF-iPSCs. Numbers indicate enrichment scores provided by DAVID. The top three clusters are colored. Blanks indicate “not listed” in the samples. The top three clusters are highlighted in blue (b) and in red (c), respectively. (d) A diagram of various GSL-biosynthetic pathways. Red and blue colors indicate genes with high and low expressions in human fibroblasts, respectively. cer: ceramide; Gb with subscript: globoside with the number of carbohydrates; G with subscript: ganglioside with subclass; Lc with subscript: lacto- with the number of carbohydrates; nLc-: neolacto-; Fuc: fucose; GalNAc: N-acetylgalactosamine; NeuAc: N-acetylneuraminic acid. (e) Individual gene-expression levels of each GSL-biosynthetic pathway in hOFs, hDFs, and hOF-iPSCs. Red and Blue indicate the same as in (d).
Mentions: At the beginning, we confirmed the expression levels of several embryonic stem cells (ESCs) markers and reprogramming factors that had been generally observed in iPSCs (Figure 2(a)). As expected, hOF-iPSCs highly expressed all pluripotent markers tested for, that is, micro RNA302a (MIR302A), MIR302B, lin-28 homolog A (LIN28A), Nanog homeobox (NANOG), developmental pluripotency associated 4 (DPPA4), glypican 4 (GPC4), prominin 1 (PROM1), growth differentiation factor 3 (GDF3), POU5F1/OCT4, and SOX2. We also found that the reprogramming factors KLF4 and c-MYC were highly expressed in hOFs and hDFs than in hOF-iPSCs. These results were consistent with previous observations [5].

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