Protein Identified That Maintains the Undifferentiated Morphology of Embryonic Stem Cells

A recent paper identified a protein called Utf1 (undifferentiated embryonic cell transcription factor 1) as being a critical to the molecular processes that maintain the undifferentiated morphology of embryonic stem cells.

Utf1 is expressed mainly in embryonic stem cells, is regulated by Oct-3/4 (octamer-binding transcription factor 3/4), and promotes rapid cell proliferation. Oct-4 also known as POU5F1 (POU domain, class 5, transcription factor 1) is a protein critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression is closely regulated, as too much or too little will cause differentiation of the cells.

The interaction of the factors that coordinate the bivalent chromatin state of embryonic stems cells so they can undergo rapid self-renewal while retaining pluripotency is only poorly understood. To shed light on these factors investigators at the Carnegie Institution for Science (Baltimore, MD, USA) used a combination of genetic, protein-oriented, and physiological approaches to study mouse embryonic stem cells.

They reported in the October 26, 2012, online edition of the journal Cell that Utf1 took part in three diverse molecular processes. First, it maintained the balance between the activation and deactivation of the genes required to direct the cell toward differentiation. Simultaneously, it inserted a molecular tag for degradation onto certain messenger RNAs. In addition, it inhibited a genetic feedback loop that normally prevents cellular proliferation, allowing this process to go forward with the rapidity that is characteristic of embryonic stem cells.

"We are slowly but surely growing to understand the physiology of embryonic stem cells," said senior author Dr. Yixian Zheng, professor of embryology at the Carnegie Institution for Science. "It is crucial that we continue to carrying out basic research on how these cells function."

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