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Ya-Ting Han, Jorn Lakowski, Mike Baron, Rachael A. Pearson, Robin R. Ali, Jane C. Sowden; Transcriptome Analysis Of Crx-expressing Photoreceptor Precursor Cells For Photoreceptor Cell Replacement Therapy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2229.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor cell transplantation is a feasible approach to rescue retinal degeneration. We demonstrated that only photoreceptor precursors, but not mature or mitotic cells are able to migrate into the adult retina and differentiate into new photoreceptors. Transplantation of early Crx-expressing precursors gives rise to both cones and rods, but shows lower levels of cells integrating into the host retina, while transplantation of late precursors gives rise to rods with higher integration levels. Our goal is to reveal the molecular similarities and differences between the early and late precursors that underlie their different transplant properties.
CrxGFP positive (+ve) and negative cells (-ve) were isolated from embryonic day (E) 15 and postnatal day (P) 4 murine retinae by flow cytometry and subjected to microarray analysis using Affymetrix Mouse Gene 1.0 arrays to identify photoreceptor precursor-specific genes. Differentially expressed genes were subjected to in silico functional and pathway analysis using DAVID and examined by quantitative PCR and immunohistochemistry.
16 genes are upregulated in E15 Crx+ve precursor cells, 494 genes in P4 precursors and 44 genes in both E15 and P4 precursors. The common precursor gene set mainly functions in transcription regulation and visual perception. The E15 precursor specific genes include 5 transcription factors Meis2, Tcfap2b, Tcfap2a, Nr2f2, Onecut1, 4 ion transporters and 2 retinol metabolisers. The P4 precursor specific genes are more diverse and include the transcription factors Nrl, Nr2e3, and Zranb1, as well as a large proportion of genes with ion binding activity. P4-specific genes are also enriched for visual perception, nucleotide binding and terms involved in cell projection, cell junction, and synapses.
We have identified genes specific for photoreceptor precursors, and genes that confer the differences between the early and late photoreceptor precursors. Analysis of these gene sets will elucidate the molecular properties that determine the different precursor cell behaviour in the developing retina and after transplantation into the adult environment.
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