28 January 2010

With a slight movement, fibroblasts turn into elegant nerve cells

Connective tissue cells were able to be directly transformed into neuronsDmitry Safin, Compulenta
Biologists from Stanford University Medical School (USA) managed to obtain fully functional neurons from mouse fibroblasts, bypassing the intermediate stage of transformation into pluripotent stem cells.

The first reports of the creation of induced pluripotent stem cells (iPSCs) date back to 2007. In those experiments, human skin cells and four transcription factors were used. A year later, it was shown that only three transcription factors were sufficient to transform one type of mouse pancreatic cells into another.

The last result made the authors think about how to exclude the intermediate stage of IPSC. Before the experiments began, they compiled a list of 19 genes potentially capable of turning cells into neurons, after which, using a lentivirus, they delivered these genes to the skin cells of mouse embryos. After 32 days, some of the cells began to resemble neurons and express the corresponding proteins.

Then the scientists began to consistently reduce the list of required genes; in its final version, only three positions remained: Ascl1, Brn2 and Myt1l. Testing of the technique on fibroblasts of adult mice showed that in less than a week about 20% of all cells turn into neurons that can perform all the functions of "ordinary": express specific proteins, generate action potential, form synapses. (In the picture, individual neurons and their clusters glow against the background of dark cells left by fibroblasts — VM.)The transition to the IPSC state takes much longer, and less than two percent of the original cells become pluripotent.

"It will be difficult to prove this, but the IPSC stage no longer seems to me to be the result of the "reverse development" of the cell and its return to its initial undifferentiated state," says study participant Marius Wernig. "Rather, it is a consequence of the same direct transformation as in our experiments."

The full version of the researchers' report is published in the journal Nature.

Prepared based on the materials of the Stanford University Medical School: Dramatic transformation: Researchers directly turn mouse skin cells into neurons, skipping IPS stage.

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