Concomitantly with RPE transdifferentiation, the transcriptional factor Mitf, an RPE specific marker, is down regulated, suggesting a change in cell fate of the injured RPE. The ectopic expres sion of Mitf is sufficient to inhibit RPE transdifferentiation, Carfilzomib Proteasome inhibitor likely inhibiting the up regulation of pax6 expression. During retina regeneration from the RPE, the newly gener ated neuroepithelium eventually differentiates into all major cell types found in the retina, and the differentiation pattern follows the same order as it does during normal develop ment. The ability of RPE cells to transdifferentiate ceases as embryonic development proceeds beyond E4. 5. How ever, the ectopic expression of pax6 is sufficient to induce RPE transdifferentiation in the intact developing chick eye up to E14.

In chick RPE cultures, overexpres sion of different pro neural transcriptional factors such as sox2, ash1, ath5, neuroD, neurogenin1, neurogenin3, cath5 and msx2 can promote the transdifferentiation of the RPE into neuronal cells. By contrast, there are several factors associated with RPE specification, including Mitf, Otx2, Wnt13, BMP Shh and Activin. The in activation of Wnt beta catenin signaling in the embryonic mouse RPE results in down regulation of RPE specific fac tors Mitf and Otx2 and expression of neural retina markers Chx10 and Rx. Recently, it has been demonstrated that somatic mam malian cells can be reprogrammed to become induced pluripotent stem cells by ectopic expression of pluripotency inducing factors Oct4, Sox2, c Myc and Klf4 as well as by the combination of Oct4, Sox2, Nanog and the RNA binding protein Lin 28.

Among all these transcrip tional factors, Oct4, Nanog and Sox2 are key factors that maintain embryonic stem cell identity. More recently, efficient differentiation of induced pluripo tent stem cells into neural retina cells has selleck screening library been demon strated, suggesting the possibility of using these cells for clinical therapies. Other studies have used a specific set of factors to convert fibroblasts directly into induced neural cells. For example, mouse fibroblasts can be directly converted into induced neural cells by overex pressing Ascl1, Brn2 and Myt1l. However, these induced cells lack the potential to generate diverse neural subtypes. In another work, transient expression of Oct4, Sox2, c Myc and Klf4 was sufficient to induce transdifferentia tion of mouse fibroblasts to neural stem progenitors cells that can be expanded and differentiate in mul tiple neuronal subtypes and glial cells.