Oct3/4 (Octamer-binding transcription factor 4), also referred to POU5F1, Oct4A, Oct3, or Oct4, is a member of the POU family of transcription factors1 expressed specifically in pluripotent cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), it plays important role in regulation of the cellular pluripotency core network[2]. O4I2, an azaindole derivative, was reported to enhance Oct3/4 activation. AZ study showed that O4I2 demonstrated the highest Oct3/4 activation in HEK-Oct3/4 reporter cells in 3.5-fold at 20 μM after 72 h of treatment; After 72 h treatment with 20 μM in HEK293 cells, the immunoblot results revealed a clear accumulation of Oct3/4 and an increased level of Nanog protein, and analysis by qRTPCR suggested a significant induction of stemness-associated genes after stimulation with O4I2, including Oct3/4, Nanog, and Sox2, while the level of Lin28 remained unaffected and Rex1 was even reduced. In human primary skin fibroblasts (HFs), qRT-PCR analysis detected a marked increase of Oct3/ 4 expression, the induction of Lin28 and Rex1 and a moderate activation of Nanog after 48 h treatment with 20 μM O4I2. Moreover, immunocytochemistry detected coexpression of Oct3/4 and Sox2 as well as Nanog and Klf4 in HF cells treated with O4I2 for 5 days. O4I2 can also promote Oct3/4 accumulation in embryonal carcinoma NCCIT cells (NCCIT-Oct3/4) and HeLa cells [3].
作用机制
O4I2 promotes Oct3/4 expression by activating its promoter site but also stabilize the Oct3/4 protein, which regulates of the cellular pluripotency core network[3].
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