MicroRNA-302 Increases Reprogramming Efficiency via Repression of NR2F2

In the 2013 study, researchers investigated the role of microRNAs (miRNAs) in cellular reprogramming, focusing on the miR-302 cluster and its interaction with transcription factors NR2F2 and OCT4. They discovered that miR-302 is highly expressed in pluripotent cells and directly targets NR2F2, which is predominantly found in differentiated cells. The study confirmed that NR2F2 inhibits OCT4 promoter activity, thereby disrupting the positive feedback loop between OCT4 and miR-302. Reprogramming human adipose-derived stem cells to induced pluripotent stem cells (iPSCs) was more efficient when miR-302 was added to the reprogramming factors KLF4, C-MYC, OCT4, and SOX2 (referred to as KMOS3) compared to the standard four factors (KMOS). Additionally, knocking down NR2F2 with shRNA enhanced reprogramming efficiency, similar to the overexpression of miR-302. However, contrary to previous reports, the researchers could not reprogram cells using only miR-302a/b/c/d. The study concludes that miR-302 promotes pluripotency by inhibiting NR2F2 and indirectly upregulating OCT4, revealing a new mechanism for inducing pluripotency in somatic cells.