A group of researchers from the Centre for Genomic Regulation in Barcelona have discovered a faster and more efficient mechanism for reprogramming induced pluripotent stem cells (iPS).
The discovery, published online in the journal Nature, decreases the time needed for cell reprogramming from a couple of weeks to a few days and reveals new information on the reprogramming process for iPS cells and their potential medical applications.
Last year, Dr. Shinya Yamanaka, together with Dr. John Gurdon, was awarded the Nobel Prize in Medicine for discovering it was possible to transform tissue cells into induced pluripotent stem cells (iPS). These cells behave in a similar way to embryonic stem cells, but can be created from differentiated adult cells. Yamanaka's discovery was groundbreaking and has great potential for regenerative medicine. The problem of this discovery is that only a very small percentage of cells can be reprogrammed, the reprogramming process takes weeks and its success rate is somewhat hit-and-miss.
Researchers from the Centre for Genomic Regulation (CRG) in Barcelona have now described a novel mechanism by which adult cells can be reprogrammed into iPS cells successfully and in a very short period of time. "Our group was using a particular transcription factor (C/EBPα) to reprogramme one type of blood cell into another (transdifferentiation). We have now discovered that this factor also acts as a catalyst when reprogramming adult cells into iPS," explains Thomas Graf, senior group leader at the CRG and ICREA research professor. "The work that we've just published presents a detailed description of the mechanism for transforming a blood cell into an iPS. We now understand the mechanics used by the cell so we can reprogramme it and make it become pluripotent again in a controlled way, successfully and in a short period of time," adds Graf.
The secret is getting to the interesting place
Genetic information is compacted into the nucleus like a skein of wool and, to access the genes, we have to untangle the ball in the region where the information we are looking for is found. What the C/EBPα factor does is temporarily open the area containing the genes responsible for pluripotency. This means that reprogramming process begins, there is no longer any room for chance; the genes involved are ready to be activated and enable the successful reprogramming of all the cells.
"We already knew that C/EBPα was related to cell transdifferentiation processes. We now know its role and why it serves as a catalyst in the reprogramming," comments Bruno Di Stefano, a PhD student in Thomas Graf's lab and first author of the work. "Following the process described by Yamanaka the reprogramming took weeks, had a very small success rate and, in addition, accumulated mutations and errors. If we incorporate C/EBPα, the same process takes only a few days, has a much higher success rate and less possibility of errors," states the young scientist.
Towards regenerative medicine
This discovery by the scientists at the CRG provides an insight into stem cell-forming molecular mechanisms, and is therefore of great interest for studies on the early stages of life, during embryonic development. At the same time, the work provides new clues for successfully reprogramming cells in humans and advances in regenerative medicine and its medical applications.
- Bruno Di Stefano, Jose Luis Sardina, Chris van Oevelen, Samuel Collombet, Eric M. Kallin, Guillermo P. Vicent, Jun Lu, Denis Thieffry, Miguel Beato, Thomas Graf. C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells. Nature, 2013; DOI: 10.1038/nature12885
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