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OAC2 is identified as an activator of octamer-binding transcription factor 4.

Octamer-binding transcription factor 4 (Oct4) has been found to be a key regulator of embryonic stem cell (ESC) pluripotency and cirtical to the reprogramming process.

In vitro: OAC2 was found to be able to activate both Oct4 and Nanog reporters to a similar extent as OAC1, which was the OAC analog showing greatest activating effects on both Oct4 and Nanog promoter-driven luciferase reporter genes. Moreover, in order to examine the developmental potential of 4F+OAC1- and 4F+OAC2-iPSCs, the authors differentiated such cells in vitro by using a standard embryoid body differentiation method. The immunostaining results showed that both the 4F+ OAC1-iPSCs and 4F+OAC2-iPSCs were able to effectively differentiate into characteristic smooth muscle actin (SMA)+ mesodermal cells, FoxA2+ endoderm cells, and Tuj1+ ectoderm cells as well [1].

In vivo: In animal to test the in vivo pluripotency of the 4F+ OAC2-induced iPSCs, the 4F+OAC2-iPSCs were transplanted the into immunodeficient Nude mice. Four to 6 weeks after transplantation, the 4F+OAC2-iPSCs could generate typical teratomas containing derivative of all three germ layers effectively, such as blood of mesoderm, intestinal epithelia of endoderm, as well as epidermis of ectoderm [1].

Clinical trial: Up to now, OAC2 is still in the preclinical development stage.

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