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Adult tissue reprogrammed into stem cells faster

7 December 2009
Appeared in BioNews 537

Researchers at the US Massachusetts Institute of Technology (MIT), lead by Professor Rudolf Jaenisch, have identified genetic pathways that can speed up the process of reprogramming mature adult cells into stem cells, known as induced pluripotent stem cells (iPS cells).

First described by Professor Shinya Yamanaka at Kyoto University in 2006, iPS cells can be generated by introducing four key stem cell genes - Oct3/4, Sox2, Klf4 and c-Myc - into adult cells. The reprogrammed cells have the same properties as embryonic stem cells (ES cells) and are pluripotent - they have the potential to grow into any other cell type in the body.

This genetic reprogramming is a slow process taking several weeks, and with low efficiency. The MIT researchers discovered that they could accelerate this process, by blocking the p53/p21 genetic pathway, or overactivating the Lin28 or Nanog genes. Altering the p53/p21 genetic pathway and the Lin28 gene reduced the amount of time to generate iPS cells, by speeding up the rate of cell divisions, whereas overactivating the Nanog gene achieved this independently of cell divisions. These two methods of accelerating the reprogramming process are distinct, and shed light on what genetic pathways are involved in reprogramming.

Published in the journal Nature, the researchers also discovered that the generation of iPS cells is a random and continuous process. They found that more than 90 per cent of cells expressing the four key stem cells genes eventually generated iPS cells. In addition, all iPS cells were identical, whether they were generated early on or after several weeks in culture. The researchers concluded that there is no subset of 'stem-like' cells in the starting material that generate iPS cells, but instead that all cells have the potential to generate iPS cells, given enough time. They demonstrated that one method of accelerating the reprogramming process is to accelerate the rate of cell divisions.

Direct cell reprogramming is a stochastic process amenable to acceleration
Nature |  3 December 2009
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12 April 2010 - by Dr Rachael Panizzo 
Researchers at the Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine have pinpointed key genetic differences between mouse embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells)....
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As 2008 drew to a close, Science magazine announced its annual top ten breakthroughs of the year, after considering novel research that 'paves the way for future discoveries'. Work in the field of cellular reprogramming was awarded pole position, ahead of a real-time video of a developing...
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Two groups of scientists have managed to 'reprogramme' skin cells, retuning them to an embryonic-like state in which they regain the potential to develop into any type of body cell. The studies, published in the journals Cell and Science, pave the way for new research aimed...
11 June 2007 - by Ailsa Stevens 
By Ailsa Taylor: Three independent research groups have reported successfully causing skin cells from adult mice to revert back to an embryonic stem cell-like state; a technique that could potentially help to resolve the ongoing ethical debate over stem cell research. Published in the journal Nature, this groundbreaking research could...
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