By ED YONG - NOT EXACTLY ROCKET SCIENCE
Added: Fri, 23 Jul 2010 03:58:42 UTC

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Imagine trying to rewind the clock and start your life anew, perhaps by moving to a new country or starting a new career. You would still be constrained by your past experiences and your existing biases, skills and knowledge. History is difficult to shake off, and lost potential is not easily regained. This is a lesson that applies not just to our life choices, but to stem cell research too.

Over the last four years, scientists have made great advances in reprogramming specialised adult cells into stem-like ones, giving them the potential to produce any of the various cells in the human body. It’s the equivalent of erasing a person’s past and having them start life again.

But a large group of American scientists led by Kitai Kim have found a big catch. Working in mice, they showed that these reprogrammed cells, formally known as “induced pluripotent stem cells” or iPSCs, still retain a memory of their past specialities. A blood cell, for example, can be reverted back into a stem cell, but it carries a record of its history that constrains its future. It would be easier to turn this converted stem cell back into a blood cell than, say, a brain cell.

The history of iPSCs is written in molecular marks that annotate its DNA. These ‘epigenetic’ changes can alter the way a gene behaves even though its DNA sequence is still the same. It’s the equivalent of sticking Post-It notes in a book to tell a reader which parts to read or ignore, without actually editing the underlying text. Epigenetic marks separate different types of cells from one another, influencing which genes are switched on and which are inactivated. And according to Kim, they’re not easy to remove, even when the cell has apparently been reprogrammed into a stem-like state.

But reprogramming adult cells is just one of two ways of making stem cells tailored to a person’s genetic make-up. The other is known as nuclear transfer. It involves transplanting a nucleus (and the DNA inside it) from one person’s cell into an empty egg. The egg becomes an embryo, which yields stem cells containing the donor’s genome. Kim has found that these cells (known as nuclear transfer embryonic stem cells or ntESCs) are much more like genuine embryonic stem cells than the reprogrammed iPSCs. They’re ‘stemmier’, for lack of a better word.
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TAGGED: GENETICS, MEDICINE