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Reprogramming Suppresses Premature Senescence Phenotypes of Werner Syndrome Cells and Maintains Chromosomal Stability over Long-Term Culture.
[werner syndrome]
Werner
syndrome
(
WS
)
is
a
premature
aging
disorder
characterized
by
chromosomal
instability
and
cancer
predisposition
.
Mutations
in
WRN
are
responsible
for
the
disease
and
cause
telomere
dysfunction
,
resulting
in
accelerated
aging
.
Recent
studies
have
revealed
that
cells
from
WS
patients
can
be
successfully
reprogrammed
into
induced
pluripotent
stem
cells
(
iPSCs
)
.
In
the
present
study
,
we
describe
the
effects
of
long
-term
culture
on
WS
iPSCs
,
which
acquired
and
maintained
infinite
proliferative
potential
for
self-renewal
over
2
years
.
After
long
-term
cultures
,
WS
iPSCs
exhibited
stable
undifferentiated
states
and
differentiation
capacity
,
and
premature
upregulation
of
senescence-associated
genes
in
WS
cells
was
completely
suppressed
in
WS
iPSCs
despite
WRN
deficiency
.
WS
iPSCs
also
showed
recapitulation
of
the
phenotypes
during
differentiation
.
Furthermore
,
karyotype
analysis
indicated
that
WS
iPSCs
were
stable
,
and
half
of
the
descendant
clones
had
chromosomal
profiles
that
were
similar
to
those
of
parental
cells
.
These
unexpected
properties
might
be
achieved
by
induced
expression
of
endogenous
telomerase
gene
during
reprogramming
,
which
trigger
telomerase
reactivation
leading
to
suppression
of
both
replicative
senescence
and
telomere
dysfunction
in
WS
cells
.
These
findings
demonstrated
that
reprogramming
suppressed
premature
senescence
phenotypes
in
WS
cells
and
WS
iPSCs
could
lead
to
chromosomal
stability
over
the
long
term
.
WS
iPSCs
will
provide
opportunities
to
identify
affected
lineages
in
WS
and
to
develop
a
new
strategy
for
the
treatment
of
WS
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated