It appears that we are discovering how to wipe out a cellsprogramming completely in preparation for reprogramming it as adifferent cell. This will allow extreme precision in eventual organreplacement. It is clearly another leap forward in our ability tomanage cell behavior.
The ultimate goal of medical research is to perfect human outcomes. Much of what we are comes up short biologically even if we do notthink so. Improving those outcomes is and will be welcome and wealready see gathering momentum develop.
Stem cells have been with us for around twenty years. This type oftech pretty well puts the controversy away.
How to make stemcells - nuclear reprogramming moves a step forward
by Staff Writers
London, UK (SPX)Oct 31, 2012
http://www.spacedaily.com/reports/How_to_make_stem_cells_nuclear_reprogramming_moves_a_step_forward_999.html
The idea of taking amature cell and removing its identity (nuclear reprogramming) so thatit can then become any kind of cell, holds great promise forrepairing damaged tissue or replacing bone marrow after chemotherapy.
Hot on the heels ofhis recent Nobel prize Dr John B. Gurdon has published in BioMedCentral's open access journal Epigenetics and Chromatin researchshowing that histone H3.3 deposited by the histone-interactingprotein HIRA is a key step in reverting nuclei to a pluripotent type,capable of being any one of many cell types.
All of an individual'scells have the same DNA, yet these cells become programmed, asthe organism matures, into different types such as heart, or lung orbrain.
To achieve thisdifferent genes are more or less permanently switched off in eachcell lineage. As an embryo grows, after a certain number ofdivisions, it is no longer possible for cells which have gone downthe pathway to become something else.
For example heartcells cannot be converted into lung tissue, and muscle cells cannotform bone.
One way to reprogramDNA is to transfer the nucleus of a mature cell into an unfertilizedegg. Proteins and other factors inside the egg alter the DNAswitching some genes on and other off until it resembles the DNA of apluripotent cell. However there seem to be some difficulties withthis method in completely wiping the cell's 'memory'.
One of the mechanismsregulating the activation of genes is chromatin and in particularhistones. DNA is wrapped around histones and alteration in how theDNA is wound changes which genes are available to the cell.
In order to understandhow nuclear reprogramming works Dr Gurdon's team transplanted a mousenucleus into a frog oocyte (Xenopus laevis). They added fluorescentlytagged histones by microinjection, so that they could see where inthe cell and nucleus the these histones collected.
Prof Gurdon explained,"Using real-time microscopy it became apparent that from 10hours onwards H3.3 (the histone involved with active genes) expressedin the oocyte became incorporated into the transplanted nucleus.
When we looked indetail at the gene Oct4, which is known to be involved in makingcells pluripotent, we found that H3.3 was incorporated into Oct4, andthat this coincided with the onset of transcription from the gene."Prof Gurdon's team also found that Hira, a protein required toincorporate H3.3 into chromatin, was also required for nuclearreprogramming.
Dr Steven Henikoff,from the Fred Hutchinson Cancer Research Center, commented,"Manipulating the H3.3 pathway may provide a way to completelywipe a cell's 'memory' and produce a truly pluripotent cell.
"Half a centuryafter showing that cells can be reprogrammed this research provides alink to the work of Shinya Yamanaka (who shared the prize), andsuggests that chromatin is a sticking point preventingartificially induced reprogramming being used routinely in theclinic."
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