Wednesday, 18 December 2013

Researchers announce new more efficient mechanism for reprogramming iPSCs

Colonies of iPCSs obtained four days after reprogramming
with Yamanaka factors,  after having expressed
 C/EBPα in B lymphocytes for 18 hours.
A team of researchers at the Centre for Genomic Regulation in Barcelona recently announced the discovery of  a faster and more efficient method for reprogramming induced pluripotent stem cells (iPSCs).

The discovery, published online in the journal Nature, decreases the time needed for cell reprogramming from a couple of weeks to just a few days, revealing new information on the reprogramming process for iPSCs 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.

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 iPSCs 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 iPSCs." explained 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 iPSCs. 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." added 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. 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." said Bruno Di Stefano, a PhD student in Thomas Graf's lab and first author of the study.

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.

- Di Stefano B, Sardina JL, van Oevelen C, Collombet S, Kallin EM, Vicent GP, Lu J, Thieffry D, Beato M, & Graf T (2013). C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells. Nature PMID: 24336202

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