ESTOOLS EU project press release
University study sheds light on human embryonic stem cells’ DNA changes
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A study on the genome of human embryonic stem cells
(hESCs) has brought scientist closer to identify and circumvent the adverse DNA
changes that naturally occur when these cells are multiplied in laboratory. The
findings could help researchers to prevent deleterious mutations in cultured
hESCs- a factor that hampers their future medical use – advancing towards application
of stem-cells-based regenerative treatments.
The collaborative study, coordinated through EU-funded
project ESTOOLS and involving experts at the University of Sheffield, is published
by the peer-review journal Nature Biotechnology, and appeared on the journal’s website on March 29th. [note: add complete reference to the article with DOI: 10.1038/nbt.1615]
Embryonic stem cells are studied for potential applications
in regenerative cell replacement therapies because of their unique capacity to
self-renew and differentiate into a variety of cell and tissue types, including
neurons, blood cells, bone and muscle.
However, it is known that genetic changes take place
in various hESC lines as they are kept multiplying in laboratory, some of which
resemble the DNA abnormalities typical of cancer cells. hESCs may also undergo
other genetic changes undetectable by conventional methods, raising concerns
for their medical use.
To address this issue, researchers used high
resolution DNA analysis to plot the genetic changes in 17 hESC lines cultured
over many generations, from the ESTOOLS consortium, the largest cluster of hESCs
laboratories in Europe. Authors of the study include several partners of ESTOOLS consortium,
including Prof Riitta Lashema and colleagues in Turku, Finland.
The study (which is the highest-resolution DNA
analysis ever done on hESCs genome) mapped hundreds
of copy number variations (CNV) and loss of heterozigosity (LOH)after prolonged
passages in culture. Both CNV and LOH are genetic variations that are usually associated with tumour transformation.
For the first time, researchers could shortlist a
number of genes that map inside or near the mutated sites, and that could therefore
be affected by these potentially deleterious changes. “When we know which genes are involved, it will be easier
to reject those hESC lines in which those genes are mutated”, says
Peter W. Andrews, from the University’s Department of Biomedical Sciences, a
leading author of the study.
Importantly, researchers found
that some hESC lines are significantly less prone to undergo genetic abnormalities
than others, which will help to select
lines that are more suitable for medical applications.
Authors point out that the
study will also help to dig into the so-called culture adaptation process, i.e.
the accumulation of genetic changes typical of malignant transformation, that
is mimicked by hESCs in culture.
Notes for editors:
For more information on
the ESTOOLS International Scientific Symposium, please visit:
www.estools.eu/Lisbon <http://www.estools.eu/Lisbon>
ESTOOLS Media Relations:
Sergio Pistoi
*NR***/ends*
