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001-es BibID:	BIBFORM049100
Első szerző:	Veréb Zoltán (immunológus, mikrobiológus, molekuláris biológus)
Cím:	Comparison of upstream regulators in human ex vivo cultured cornea limbal epithelial stem cells and differentiated corneal epithelial cells / Zoltán Veréb, Réka Albert, Szilárd Póliska, Ole Kristoffer Olstad, Saeed Akhtar, Morten C. Moe, Goran Petrovski
Dátum:	2013
ISSN:	1471-2164
Megjegyzések:	BACKGROUND:The surface of the human eye is covered by corneal epithelial cells (CECs) which regenerate from a small population of limbal epithelial stem cells (LESCs). Cell therapy with LESCs is a non-penetrating treatment for preventing blindness due to LESC deficiency or dysfunction. Our aim was to identify new putative molecular markers and upstream regulators in the LESCs and associated molecular pathways.RESULTS:Genome-wide microarray transcriptional profiling was used to compare LESCs to differentiated human CECs. Ingenuity-based pathway analysis was applied to identify upstream regulators and pathways specific to LESCs. ELISA and flow cytometry were used to measure secreted and surface expressed proteins, respectively. More than 2 fold increase and decrease in expression could be found in 1830 genes between the two cell types. A number of molecules functioning in cellular movement (381), proliferation (567), development (552), death and survival (520), and cell-to-cell signaling (290) were detected having top biological functions in LESCs and several of these were confirmed by flow cytometric surface protein analysis. Custom-selected gene groups related to stemness, differentiation, cell adhesion, cytokines and growth factors as well as angiogenesis could be analyzed. The results show that LESCs play a key role not only in epithelial differentiation and tissue repair, but also in controlling angiogenesis and extracellular matrix integrity. Some pro-inflammatory cytokines were found to be important in stemness-, differentiation- and angiogenesis-related biological functions: IL-6 and IL-8 participated in most of these biological pathways as validated by their secretion from LESC cultures.CONCLUSIONS:The gene and molecular pathways may provide a more specific understanding of the signaling molecules associated with LESCs, therefore, help better identify and use these cells in the treatment of ocular surface diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Limbal epithelial stem cells Corneal epithelial cells Gene array Upstream regulators Cytokines Cell adhesion IL-6 IL-8 Angiogenesis
Megjelenés:	BMC Genomics. - 14 : 1 (2013), p. [1-33]. -
További szerzők:	Albert Réka (1986-) Póliska Szilárd (1978-) (biológus) Olstad, Ole Kristoffer Akhtar, Saeed (1949-) (molekuláris biológus) Moe, Morten C. Petrovski, Goran (1975-) (orvos)
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