Kraniyosinostozlarda Primer Fibroblast Kültüründe Transkriptom Çalışması

Abstract

Çetinkaya A. Transcriptome study in primary fibroblast cultures in craniosynostosis. Hacettepe University, Faculty of Medicine, Medical Genetics Specialty Thesis, Ankara 2014. Cranial sutures are unossified connective tissue structures between the cranial bones, which allow the expansion of these bones during development. Premature ossification of these structures is called craniosynostosis. Apert Syndrome is an autosomal dominantly inherited syndrome, which is characterized by craniosynostosis, other skeletal anomalies and dysmorfic findings, as well as other systemic abnormalities. Two missense mutations in FGFR2 gene which result in ligand-dependent gain of function is responsible for most of Apert Syndrome in affected individuals. In this study, primary skin fibroblast cultures obtained from 3 individuals with Apert Syndrome and 3 controls without craniosynostosis were compared with transcriptome microarray. In addition, primary fibroblast response to FGF2 was evaluated. As a result, 181 genes were shown to be differentially expressed between experimental groups. Among these 181 genes, 10 genes, which significantly differ in Apert Syndrom fibroblasts compared to controls, were shown to be involved in a common interaction network and have common GO terms. Among these COL11A1, COMP, CPXM2, ITGA8, MGF and TNC are related with extracellular matrix organization and FRZB, SFRP2, TBX5 and WNT are related with mesenchymal differentiation. Upregulation of both pathways show that Apert Syndrome primary fibroblast cultures have an increased tendency towards bone differentiation. The results of this study have supported the notion that craniosynostosis in Apert Syndrome is the result of fast and early differentiation of connective tissue in the sutures. Furthermore, this study demonstrates the potential of using primary dermal fibroblast cultures as a model in research related to Apert Syndrome.