Oct4 is a key regulator for ESC (embryonic stem cell) pluripotency. Reduced expression of Oct4 results in differentiation of ESCs into trophectodermal cells, and ovexpression of Oct4 leads to differentiation of ESCs along the mesodermal and primitive endodermal lineages. OAC1 (Oct4-activating compound 1), was found to activate both Oct4 and Nanog promoter-driven luciferase reporter genes. By counting the number of clones with ESC-like morphology at day 18, it was found that both OAC1 enhanced the 4F (a transcription factor quartet)-induced reprogramming efficiency considerably. The number of colonies with ESC-like morphology increased two fold or more in 4F plus OAC (4F+OAC) treatment, compared with the 4F treatment alone. Furthermore, addition of OAC1 to the reprogramming mixture considerably accelerated the appearance of iPSC-like colonies. Treatment of compound OAC1 started on day 1 and lasted for 7 d. Many GFP+ single cells were seen in treated cells at day 2 and the GFP+ colonies started to appear at day 3. At day 5, a more than threefold increase in the number of GFP+ colonies was detected in OAC1-treated, 4F-transduced cells (4F+OAC1), compared with vehicle-treated, 4F-transduced cells. At day 8, an approximately fourfold increase in the number of GFP+ colonies were observed in 4F+OAC1-treated cells (2.75% reprogramming efficiency), compared with 4F-treated cells (0.68% efficiency)[2].
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