02 March 2010

Nature: hits of the last number – reprogrammed cells

The most interesting (according to the reviewer of the Genomeweb site) of the articles in the field of life sciences from the latest issue of the journal Nature, dated 25.02.2010, are devoted to the reprogramming of somatic cells into induced pluripotent ones.

Scientists from Stanford University have found a simple and fast way to convert mouse fibroblasts into functional neurons in cell cultures. In the article Direct conversion of fibroblasts to functional neurons by defined factors, researchers led by Marius Wernig demonstrated that the simultaneous production of Asc11, Brn2 and Myt11 proteins in mouse embryonic and postnatal fibroblasts leads to their transformation into functional neurons producing characteristic neuron-specific proteins and capable of forming functional synapses. The technique proposed by the authors may be useful for studying the process of formation of neurons; it can be used as a model system for the study of nervous diseases; its application in regenerative medicine is also possible.

The reprogramming of somatic cells into induced pluripotent stem cells capable of differentiating into cells of all types of tissues of an adult organism can make a revolution in regenerative medicine. Obtaining induced pluripotent cells using known reprogramming techniques is associated with a number of difficulties: the process usually takes about 2-3 weeks, cells grow asynchronously, and a significant part of the DNA in them is methylated and therefore inactive. In the article Reprogramming towards pluripotency requires AID-dependent DNA demethylation, another group of researchers from Stanford, working under the leadership of Helen Blau, demonstrated that in interspecific heterokaryons (binuclear cells from mouse stem cells and human fibroblasts) quickly (in one day), synchronously and efficiently (about 70%) reprogramming into a pluripotent state is induced. With the help of knockdown (temporary suppression of protein production) of the AID gene (also called AICDA), the researchers found that the AID protein is necessary for DNA demethylation, making DNA available for the production of appropriate proteins, and initiating the process of reprogramming human somatic cells into a pluripotent state.

In another article, Tbx3 improves the germ-line competence of induced pluripotent stem cells, an international group of scientists managed to discover the Tbx3 protein that improves the quality and competence of induced pluripotent stem cells. Determination of the binding sites of the transcription factor Tbx3 with the genomic DNA of embryonic stem cells allowed researchers to establish the participation of this protein in the regulation of the activity of genes encoding reprogramming factors, such as Oct4, Sox2, Nanog and Smad1. The scientists also found that induced pluripotent stem cells obtained using reprogramming factors OSK and Tbx3 proved to be the most suitable for obtaining germ cells. The study, according to its authors, emphasizes the need for a more thorough analysis of the resulting induced pluripotent stem cells outside of in vitro experiments.

Daria Chervyakova
Portal "Eternal youth" http://vechnayamolodost.ru based on Genomeweb materials: This Week in Nature02.03.2010

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