Figure 7

Schematic representation of putative re-programming of CE stem cells in vitro . In vivo exposure of adult CE to exogenous growth factors (GF) such as FGF2 and insulin promotes proliferation of quiescent CE stem cells and some of them express Pax6 [45]. Whether or not these cells are capable of generating neurons or more specifically retinal cells is not well known. These cells, when cultured in the presence of mitogens, generate neurospheres accompanied by a decrease in the expression of CE-specific genes and the acquisition of the expression of genes corresponding to retinal progenitors, representing the first stage of reprogramming. The resulting neurospheres consists of heterogeneous population of cells with subsets, which are BrdU positive, and express pan neural and retinal progenitor markers. The frequency of CE cells capable of generating neurospheres is 1 in 600 mouse and 500 rat CE cells, as determined by LDA analyses [1, 4]. Cells in neurospheres have the potential to respond to specific cues for retinal differentiation. Therefore, depending upon the cues, they activate expression of regulatory genes for rod photoreceptors (e.g., Nrl) or RGCs (e.g., Atoh7) to differentiate along specific retinal sub-lineages, representing the second stage of reprogramming. The efficiency and fidelity of retinal lineage conversion will be influenced by the efficiency of reprogramming at both stages. Since the reprogramming is non-cell autonomous, its efficiency will directly depend upon culture conditions, the variability in which might have led to contradictory results.