Grigory Ryzhakov – Russian Writer

Nobel 2012: Stem Cell, Cloning and the DNA State

A scheme of animal cloning (converted to SVG by Belkorin, modified and translated by Wikibob [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC-BY-SA-3.0 (http://creativecommons.org/licenses/by-sa/3.0/)], via Wikimedia Commons)

The first science Nobel Prizes were awarded this week.  John B. Gurdon of the University of Cambridge in England and Shinya Yamanaka of Kyoto University in Japan received the prize in Physiology and Medicine for their work showing how it’s possible for a mature cell of the body to revert to a state similar to embryonic.

John Gurdon‘s  initial ground-breaking work is over 50 years old now. He cloned a first animal, which was a frog:  by taking a nucleus out  from a frog’s gut cell and putting it into a frog’s egg, which had its own nucleus removed, Gurdon observed this new egg  living, dividing , growing first into an embryo and eventually becoming a tadpole. In 1997 a similar technique was used to clone the famous sheep Dolly.

Initially, Gurdon’s work was met sceptically because of the common view that the cell commitment to a specific function in the body was irrevocable. For years, until the onset of genomic era, it was impossible to understand how components of the egg would reprogram the nucleus of the somatic cell to make it work like a nucleus of a developing egg. But then the molecular biology came into view.

The cell nucleus is a tiny room where the whole genome in the form of chromosomes is tightly packed.  In my post on immortality I’ve mentioned that chromosomes are single extremely long DNA molecules, containing thousands of genes. Because of their length they need to be tightly packed in an orderly manner by specialised proteins, and they need to be accessible to other proteins, which transcribe genes into gene products required for various cellular functions.

What is the difference between chromosomes of an egg and a gut cell? The chromosomes of the developing egg are far more open and accessible to proteins to enable the egg to divide and differentiate into embryonic cells, which would give rise to all the tissues.  Such cells are called pluripotent stem cells, they can turn into any cell type. The  chromosomal DNA of the gut cell is  only accessible in a way that ensures it to stay a gut cell and renders it unable to turn into another cell type. In layman’s terms the gut cell’s nucleus has many genes closed  and the specific genes open to keep the gut cell identity under bay.

This is controlled by a chemical modification of DNA called methylation:  if a particular part of the chromosomal DNA is methylated, it gets closed, inaccessible, by being associated with special proteins marking it for storage and not for use.  Of course, this is an oversimplification, the special proteins I’ve mentioned are chemically modified too. The biological discipline studying all these modifications of DNA and the associated proteins and how they affect the cell processes and inheritance is called epigenetics. I shall definitely blog about it another time.

For now the question is – so what? Okay, we found what makes cells different from each other, what’s the use?

In 2006 Shinya Yamanaka published a study showing how to transform a regular committed cell from the body into a pluripotent cell able to give rise to any other cell types.  He called these cells induced pluripotent stem (iPS) cells. To get an iPS, he introduced a minimal set of four genes, encoding DNA-binding proteins called transcription factors, into a somatic cell.

The benefits of iPS are obvious, – regenerative medicine.  If one needs transplantation, the required tissue or organ can be produced out of such iPS cells coming from the patient’s own skin cells. This way one would avoid a transplant rejection by the immune system and there would be no need to use the health-wrecking immuno-suppressive drugs.

However, my rambling about open/close genes wasn’t just for the show-off effect. The first  iPS cell line Yamanaka created showed wrong DNA methylation patterns (meaning the pattern of Openness/Closedness of the chromatin) compared to normal embryonic stem cells, and these  iPS stem cells were not fully functional.  There were other complications with these iPS cells, which you can read about in here.

Still, the iPS research moves forward quickly, these cells are becoming better and the therapeutic application is hopefully not beyond the horizon anymore.

To me, the most important contribution Gurdon and Yamanaka made is that they advanced our understanding of how cells commit to their fate (how they become mortal  as opposed to immortal stem cells)  at the level of chromosomal DNA.

P.S. It’s Friday, it’s my birthday and I can choose not to proofread my post, ho ho ho!

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  • Ashen

    Happy birthday, Grisha 🙂

    Thanks for the post. Fantastic. I’m glad to hear Stem Cell research is making progress. This will bring fresh hope for many people with spinal injuries. A dear friend of mine struggled for two years to regain movement after a fall, much encouraged by the work on Stem Cells. Sadly, she did not survive an infection she picked up in hospital. She would have been cheered by the news.

    • GrigoryRyzhakov

      thank you for greetings, Ashen! Yes, I’m very excited about the stem cells progress and luckily all the human cloning bans don’t cover stem cells, as they are coming from adults.
      I’m sorry about your friend, – alas we are mortal and even if we crack the longevity code we’ll still die of injuries and infections, though less often than now. But there will be a different issue – how would the society cope with immortality, how would it avoid overpopulation, how the longevity would influence people’s sanity? This is a big issue I think to explore in the modern literature before it becomes a reality, it deserves writer’s attention much more than basic sexual, gastronomic, you name it human urges do (I hint on a certain book series here lol)