Human Embryonic Stem Cells Derived From Preimplantation Genetically
Diagnosed Embryos
ScienceDaily (Nov. 15, 2007) — A human stem cell line derived from
embryos that were identified by preimplantation genetic diagnosis
(PGD) to carry the mutation for fragile X syndrome has provided an
unprecedented view of early events associated with this disease. In
addition to giving scientists fresh insight into fragile X, results
from this unique model system have emphasized the value of this new
source of embryonic stem cells and may have a significant impact on
the way that genetic diseases are studied in the future.
Fragile X syndrome, the most common cause of inherited mental
impairment and of autism, is caused by the absence of the fragile X
mental retardation protein (FMRP). Most individuals with fragile X
exhibit a specific mutation in the fragile X mental retardation 1
(FMR1) gene that usually coincides with epigenetic DNA modifications.
However, the developmental timing and mechanisms associated with
acquisition of these characteristics are not clear due to the absence
of appropriate cellular and animal models.
To examine developmentally regulated events involved in fragile X
pathogenesis, Dr. Nissim Benvenisty and Dr. Rachel Eiges from the
Hebrew University Department of Genetics in Jerusalem, Israel,
together with Dr. Dalit Ben-Yosef from the IVF unit at the Tel-Aviv
Sourasky Medical Center, established a human embryonic stem cell
(HESC) line from a preimplantation fragile X-affected embryo
identified by PGD. The fragile X cell line, called HEFX, displayed
all characteristics typical of an HESC line and possessed the full
genetic mutation observed in fragile X patients.
The researchers found that undifferentiated HEFX cells transcribed
FMR1 and expressed FMRP, suggesting that the fragile X mutation by
itself is not sufficient to cause FMR1 inactivation. The research
team went on to show that differentiated derivatives of HEFX cells
exhibited a decrease in FMRI transcription and FMRP expression along
with an increase in epigenetic modifications associated with fragile
X syndrome. "The fact that FMR1 inactivation and other modifications
take place after differentiation suggests that it might be possible
to prevent some of these events as an attempt to rescue the abnormal
phenotype in cells with the full fragile X mutation," suggests Dr.
Benvenisty.
HEFX cells represent an excellent model for examination of early
embryogenesis and will contribute to a clearer understanding of the
molecular mechanisms underlying fragile X pathogenesis. This research
is also compelling on a more general level in that it validates the
usefulness of HESCs derived from embryos that have been screened for
specific mutations with PGD. ESC lines derived in this manner
represent a potent tool for the study of a variety of human diseases
and the development of new therapeutic strategies.
The research is published in the November issue of the journal Cell
Stem Cell, published by Cell Press.
The researchers include Rachel Eiges, Achia Urbach, Amir Eden, Ofra
Yanuka, andNissim Benvenisty, of the Silberman Institute of Life
Science, The Hebrew University, Jerusalem, Israel; Mira Malcov, Tsvia
Frumkin, Tamar Schwartz, Dalit Ben-Yosef, Ami Amit, and Yuval Yaron,
of the Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine,
Tel Aviv University, Tel-Aviv, Israel.
Adapted from materials provided by Cell Press.
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MLA Cell Press (2007, November 15). Human Embryonic Stem Cells
Derived From Preimplantation Genetically Diagnosed Embryos.
ScienceDaily. Retrieved November 15, 2007, from
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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