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Gene expression changes between patent and fused cranial sutures in a nonsyndromic craniosynostosis population.

Potter AB, Rhodes JL, Vega RA, Ridder T, Shiang R - Eplasty (2015)

Bottom Line: SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures.SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

View Article: PubMed Central - PubMed

Affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland.

ABSTRACT

Objective: Craniosynostosis is a premature fusion of 1 or more cranial sutures. It may occur with additional morphological abnormalities (syndromic) or in isolation. Studies suggest that dysregulation of normal cell proliferation, differentiation, and migration has a role in isolated or nonsyndromic craniosynostosis but the molecular mechanisms remain unknown. The aim of this research is to identify genes differentially expressed in prematurely fused human suture compared to patent suture in nonsyndromic craniosynostosis.

Methods: Bone fragments from synostosed and patent sutures of 7 infants with nonsyndromic craniosynostosis were collected during surgical release of fused sutures. RNA was isolated from the fragments (7 patent and 7 fused) and global gene expression profiled using the Illumina WGE-DASL assay and HumanRef 8.0 Beadchip.

Results: Comparison of mRNA expression in fused and patent suture identified 68 genes significantly differentially expressed and having fold changes ≤ -2.0 and ≥ 2.0 with a false discovery rate adjusted P value at .10 and 136 with adjusted P value of 0.15. SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures. Analysis including only sagittal fused sutures revealed a set of 35 overlapping genes that may be involved in suture patency over all suture types. SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.

Conclusion: Differentially expressed genes were identified in fused suture relative to patent in a nonsyndromic craniosynostosis population. SFRP2 is likely important in suture patency. Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

No MeSH data available.


Related in: MedlinePlus

Heat map and hierarchical clustering. Clustering of individual suture samples using significantly differentially expressed genes. Individual suture samples are listed on the left with patient numbers (Table 1) and P referring to patent sutures and F to fused sutures.
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Figure 3: Heat map and hierarchical clustering. Clustering of individual suture samples using significantly differentially expressed genes. Individual suture samples are listed on the left with patient numbers (Table 1) and P referring to patent sutures and F to fused sutures.

Mentions: Even though our samples were derived from only NSC individuals, we used different patent and fused suture type combinations in this study as well as samples from both male and female individuals. To determine whether this combination of different suture type tissue is an issue, we used hierarchical clustering with our significantly differentially expressed genes across samples (Fig 3). We found that in all but 1 case, the expression of the fused sutures cluster together as well as the patent suture irrespective of suture type or gender. In general, neither suture type nor sex clustered together within a group (patent vs fused). The 1 exception was individual 7, whose fused suture clustered with the patent suture group most closely with patent suture from patient 4, the only sagittal patent suture studied.


Gene expression changes between patent and fused cranial sutures in a nonsyndromic craniosynostosis population.

Potter AB, Rhodes JL, Vega RA, Ridder T, Shiang R - Eplasty (2015)

Heat map and hierarchical clustering. Clustering of individual suture samples using significantly differentially expressed genes. Individual suture samples are listed on the left with patient numbers (Table 1) and P referring to patent sutures and F to fused sutures.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401998&req=5

Figure 3: Heat map and hierarchical clustering. Clustering of individual suture samples using significantly differentially expressed genes. Individual suture samples are listed on the left with patient numbers (Table 1) and P referring to patent sutures and F to fused sutures.
Mentions: Even though our samples were derived from only NSC individuals, we used different patent and fused suture type combinations in this study as well as samples from both male and female individuals. To determine whether this combination of different suture type tissue is an issue, we used hierarchical clustering with our significantly differentially expressed genes across samples (Fig 3). We found that in all but 1 case, the expression of the fused sutures cluster together as well as the patent suture irrespective of suture type or gender. In general, neither suture type nor sex clustered together within a group (patent vs fused). The 1 exception was individual 7, whose fused suture clustered with the patent suture group most closely with patent suture from patient 4, the only sagittal patent suture studied.

Bottom Line: SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures.SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

View Article: PubMed Central - PubMed

Affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland.

ABSTRACT

Objective: Craniosynostosis is a premature fusion of 1 or more cranial sutures. It may occur with additional morphological abnormalities (syndromic) or in isolation. Studies suggest that dysregulation of normal cell proliferation, differentiation, and migration has a role in isolated or nonsyndromic craniosynostosis but the molecular mechanisms remain unknown. The aim of this research is to identify genes differentially expressed in prematurely fused human suture compared to patent suture in nonsyndromic craniosynostosis.

Methods: Bone fragments from synostosed and patent sutures of 7 infants with nonsyndromic craniosynostosis were collected during surgical release of fused sutures. RNA was isolated from the fragments (7 patent and 7 fused) and global gene expression profiled using the Illumina WGE-DASL assay and HumanRef 8.0 Beadchip.

Results: Comparison of mRNA expression in fused and patent suture identified 68 genes significantly differentially expressed and having fold changes ≤ -2.0 and ≥ 2.0 with a false discovery rate adjusted P value at .10 and 136 with adjusted P value of 0.15. SFRP2 (secreted frizzled-related protein 2) demonstrated the largest decrease in fused sutures. Analysis including only sagittal fused sutures revealed a set of 35 overlapping genes that may be involved in suture patency over all suture types. SPHKAP (sphingosine kinase type 1-interacting protein), a modulator of TGFβ signaling, was significant in the sagittal subset.

Conclusion: Differentially expressed genes were identified in fused suture relative to patent in a nonsyndromic craniosynostosis population. SFRP2 is likely important in suture patency. Genes having significant roles in osteoblastogenesis as negative regulators of canonical Wnt pathway were significantly downregulated.

No MeSH data available.


Related in: MedlinePlus