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Goran Petrovski, Reka Albert, Zoltan Vereb, Morten Moe, Ole Kristoffer Olstad, Andras Berta, Laszlo Fesus; Comparative gene expression analysis of human cornea limbal epithelial stem cells and differentiated corneal epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):997.
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© ARVO (1962-2015); The Authors (2016-present)
Limbal epithelial stem cells (LESCs) are responsible for corneal epithelium regeneration. Specific molecular markers for LESCs have not been well defined. Our goal was to find new putative markers for these cells and to identify associated molecular pathways.
Limbal tissue explants and central corneal epithelium were harvested from cadavers (according to the Guidelines of the Helsinki Declaration). The explants were cultured ex vivo and expanded into LESCs in a human serum containing medium. Genome-wide microarray analysis was performed using Affymetrix GeneChip Human Gene 1.0 ST Array containing more than 28,000 gene transcripts. Functional analysis using Ingenuity software was carried out to identify pathways and molecules specific for LESCs.
LESCs showed upregulated expression of 10 top molecules (flavin containing monooxygenase (FMO) 1 and 2, fibronectin 1 (FN1), kallikrein (KLK) 6 and 7, transcobalamin 1 (TCN1), semaphorin 3A (SEMA3A), annexin A3 (ANXA3), V-set domain-containing T-cell activation inhibitor 1 (VTCN1) and heat shock protein beta-8 (HSPB8), and downregulated expression of cartilage acidic protein 1 (CRTAC1), alcohol dehydrogenase class 4 mu/sigma chain (ADH7), hepatic leukemia factor (HLF), CD36, Doublecortin domain containing 5 (DCDC5), Diacylglycerol kinase beta (DGKB), protein prune homolog 2 (PRUNE2), anoctamin 4 (ANO4), death associated protein-like 1 (DAPL1) and carbonic anhydrase (CA6) compared to differentiated corneal epithelium (p<0.05). Cannonical pathways specific for LESCs, including RAR activation, antigen presentation and axonal guidance signaling could be identified (p<0.001). A number of molecules functioning in cellular movement (381), proliferation (567), development (552), death and survival (520), and cell-to-cell signaling (290) were found with top biological functions in LESCs (p<0.001). In addition, 5 upstream regulators could be identified in LESCs (TGFB1, TNF, IFNG, ERBB2 and OSM).
Gene and molecular pathways may provide more specific understanding of the signaling molecules associated with LESCs. Future better identification and use of LESCs in treatment of ocular surface diseases and discovery of innovative therapies may be aided by gene array technology.
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