Wednesday, 6 February 2013

New insight on Oct3 and its role in iPSCs creation

A few hours ago, a team of researchers from the The European Molecular Biology Laboratory (EMBL) and from the Max Planck Institute for Molecular Biomedicine (MIMB) released a new study that revealing new insight regarding the transcription factor Oct4 protein and its role in the creation of induced pluripotent stem cells from somatic cells.

As we explain in our iPSCs article, Oct4 (along with Sox2, Klf4 and c-Myc) is one of the main proteins used for controlling and reprogramming certain genes that in return cause somatic cells to revert into a stem cell-like pluripotent nature. The researchers from EMBL, led by Matthias Wilmann, used X-ray technology and suffesfully managed to resolve the crystal structure of Oct4. Their study is focused on a, previously unknown linker between two Oct4 binding elements. According to Wilmann, the link's unique nature had intrigued them for more than a decade. Now their findings finally shed some new light,suggesting that the linker recruits key partners to the Oct4 target genes which are crucial for inducing somatic cells to become iPSCs.

Further studies on the modifications of the linker from the MIMB associates, led by Hans Schöle, confirmed the findings of the EMBL researchers. Their findings showed that when the sequence was altered, the OCT4 lost its reprogramming potential. Even the smallest changes in the link sequence, had a major impact on the protein's interface, seriously affecting its ability to recruit key partners.

Schöler said that their study reveals the unique nature of the Oct interface, and how it contributes in the reprogramming process involved in the creation of induced pluripotent stem cells. He believes that the study is a great step towards a better understanding of the mechanisms involved in cell reprogramming, concluding that the study may have implications in the fields of drug research and tissue engineering.

Informational video about induced pluripotent stem cells, by iPSCs pioneer Shinya Yamanaka 

Esch D, Vahokoski J, Groves MR, Pogenberg V, Cojocaru V, Vom Bruch H, Han D, Drexler HC, Araúzo-Bravo MJ, Ng CK, Jauch R, Wilmanns M, & Schöler HR (2013). A unique Oct4 interface is crucial for reprogramming to pluripotency. Nature cell biology PMID: 23376973

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