Proteomic differentiation between murine retinal and brain-derived progenitor cells.

ABSTRACT

Previous studies have transplanted a variety of neural stem cells (NSCs) to the eye in hopes of developing a therapy to replace retinal neurons lost to disease. Successful integration, survival, and differentiation of the cell types has been variably successful. At the moment, little is known about the fundamental biological differences between stem cell or progenitor cell types. Characterization of these differences will not only increase our general understanding of this broadly characterized group of cells, but also lead to development of criteria for sorting cells, evaluating their differentiation, and predicting their suitability for transplantation. We have used two-dimensional gel electrophoresis protein expression profiles to characterize the molecular differences between two populations of murine progenitor cells-retinal progenitor cells (RPCs) and brain progenitor cells (BPCs) isolated from mice of the same age and same genetic background. Our protein expression profiling identified 22 proteins that are differentially expressed in RPCs when compared to BPCs. Four of the differentially expressed proteins correspond to proteins known to be involved in a cellular response to stress, and analysis of potential transcription factor binding sites in the promoter regions of their genes suggests these proteins could be co-regulated at the transcriptional level. On the basis of this discovery, we tested the hypothesis that the addition of the antioxidant vitamin E would decrease the expression of the stress-response proteins and influence differentiation of RPCs. Further investigation of differences between multiple populations of RPCs and BPCs during their maintenance and differentiation will further identify fundamental differences that define 'retinal-like' characteristics and provide tools to assay the success of efforts to influence many populations of stem cells to adapt a retinal cell fate.