Pluripotent stem cells: even faster and more efficient
A big Step towards efficient Cell Reprogramming
LifeSciencesToday based on CRG materials: A big step for cell reprogrammingA group of scientists from the Barcelona Center for Genomic Regulation (Centro de Regulacion Genomica, CRG) has developed a faster and more efficient method for producing induced pluripotent stem cells.
Their discovery, published online in the journal Nature (Bruno Di Stefano et al., C/EBPalfa poises B cells for rapid reprogramming into induced pluripotent stem cells), reduces the time required for cell reprogramming from several weeks to several days and provides new information about the process of reprogramming induced pluripotent stem cells and their potential use in medicine.
Last year, Dr. Shinya Yamanaka, together with Dr. John Gurdon, was awarded the Nobel Prize in Medicine for discovering the possibility of transforming specialized tissue cells into induced pluripotent stem cells (iPSCs). These cells behave similarly to embryonic stem cells, but can be created from differentiated adult cells. Dr. Yamanaka's discovery has a huge potential for the development of regenerative medicine, but several obstacles prevent the practical use of the results obtained by him: a very small percentage of cells can be reprogrammed, and the reprogramming process itself takes weeks and, very importantly, is largely random.
Researchers from the Center for Genomic Regulation have described a new mechanism by which adult cells can be successfully reprogrammed into iPSCs in a very short period of time.
"Our group has already used a special transcription factor (C/EBPalfa) to reprogram one type of blood cells into another – transdifferentiation. Now we have established that this factor acts as a catalyst for reprogramming adult cells in iPSCs," explains the head of the work, Research Professor Thomas Graf. "The paper we have just published provides a detailed description of the mechanism of transformation of a blood cell into an iPS cell. Now we understand the mechanism used by the cell and can reprogram it and make it pluripotent again – in a controlled, effective and short time."
Colonies of pluripotent cells obtained four days after reprogramming by Yamanaki factors
and 18 hours of C/EBPalfa expression in B lymphocytes. (Photo: Centre for Genomic Regulation)
Genetic information is tightly packed in the cell nucleus, and in order to access the genes, you need to untangle this "skein of wool" in the area where the necessary information is located. Factor C/EBPalfa temporarily opens up a region containing genes responsible for pluripotency. This means the beginning of the reprogramming process, and there is no more place for randomness; the genes involved in it are ready to activate and make possible the successful reprogramming of all cells.
"We already knew that C/EBPalfa is associated with the process of cell transdifferentiation. Now we know its role and why it is a catalyst for reprogramming," comments Bruno Di Stefano, PhD student in Thomas Graf's laboratory, the first author of the article. "The reprogramming process described by Yamanaka takes weeks, has very low efficiency and, in addition, goes with the accumulation of mutations and errors. When using C/EBPalfa, the same process takes only a few days, has a much higher efficiency and a lower probability of errors," says the young scientist.
The discovery of scientists from CRG deepens our understanding of the molecular mechanisms of stem cell formation and is of great interest from the point of view of studying the early stages of life during embryonic development. At the same time, this work provides new keys to the successful reprogramming of human cells and to further achievements in the field of theoretical and practical regenerative medicine.
Portal "Eternal youth" http://vechnayamolodost.ru17.01.2014