It appears that we are discovering how to wipe out a cells
programming completely in preparation for reprogramming it as a
different cell. This will allow extreme precision in eventual organ
replacement. It is clearly another leap forward in our ability to
manage 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 not
think so. Improving those outcomes is and will be welcome and we
already see gathering momentum develop.
Stem cells have been with us for around twenty years. This type of
tech pretty well puts the controversy away.
How to make stem
cells - nuclear reprogramming moves a step forward
by Staff Writers
London, UK (SPX) Oct 31, 2012
The idea of taking a
mature cell and removing its identity (nuclear reprogramming) so that
it can then become any kind of cell, holds great promise for
repairing damaged tissue or replacing bone marrow after chemotherapy.
Hot on the heels of
his recent Nobel prize Dr John B. Gurdon has published in BioMed
Central's open access journal Epigenetics and Chromatin research
showing that histone H3.3 deposited by the histone-interacting
protein 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's
cells have the same DNA, yet these cells become programmed, as
the organism matures, into different types such as heart, or lung or
brain.
To achieve this
different genes are more or less permanently switched off in each
cell lineage. As an embryo grows, after a certain number of
divisions, it is no longer possible for cells which have gone down
the pathway to become something else.
For example heart
cells cannot be converted into lung tissue, and muscle cells cannot
form bone.
One way to reprogram
DNA is to transfer the nucleus of a mature cell into an unfertilized
egg. Proteins and other factors inside the egg alter the DNA
switching some genes on and other off until it resembles the DNA of a
pluripotent cell. However there seem to be some difficulties with
this method in completely wiping the cell's 'memory'.
One of the mechanisms
regulating the activation of genes is chromatin and in particular
histones. DNA is wrapped around histones and alteration in how the
DNA is wound changes which genes are available to the cell.
In order to understand
how nuclear reprogramming works Dr Gurdon's team transplanted a mouse
nucleus into a frog oocyte (Xenopus laevis). They added fluorescently
tagged histones by microinjection, so that they could see where in
the cell and nucleus the these histones collected.
Prof Gurdon explained,
"Using real-time microscopy it became apparent that from 10
hours onwards H3.3 (the histone involved with active genes) expressed
in the oocyte became incorporated into the transplanted nucleus.
When we looked in
detail at the gene Oct4, which is known to be involved in making
cells pluripotent, we found that H3.3 was incorporated into Oct4, and
that this coincided with the onset of transcription from the gene."
Prof Gurdon's team also found that Hira, a protein required to
incorporate H3.3 into chromatin, was also required for nuclear
reprogramming.
Dr Steven Henikoff,
from the Fred Hutchinson Cancer Research Center, commented,
"Manipulating the H3.3 pathway may provide a way to completely
wipe a cell's 'memory' and produce a truly pluripotent cell.
"Half a century
after showing that cells can be reprogrammed this research provides a
link to the work of Shinya Yamanaka (who shared the prize), and
suggests that chromatin is a sticking point preventing
artificially induced reprogramming being used routinely in the
clinic."
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