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Tbx1 modulates endodermal and mesodermal differentiation from mouse induced pluripotent stem cells.
[22q11.2 deletion syndrome]
The
T
-
box
transcriptional
factor
(
Tbx
)
family
of
transcriptional
factors
has
distinct
roles
in
a
wide
range
of
embryonic
differentiation
or
response
pathways
.
Tbx
1
,
a
T
-
box
transcription
factor
,
is
an
important
gene
for
the
human
congenital
disorder
22
q
11
.
2
deletion
syndrome
.
Induced
pluripotent
stem
cell
(
iPSC
)
technology
offers
new
opportunities
for
both
elucidation
of
the
pathogenesis
of
diseases
and
the
development
of
stem-cell-based
therapies
.
In
this
study
,
we
generated
iPSCs
from
Tbx
1
(
-
/
-
)
and
Tbx
1
(
+
/
+
)
fibroblasts
and
investigated
the
spontaneous
differentiation
potential
of
iPSCs
by
detailed
lineage
analysis
of
the
iPSC-derived
embryoid
bodies
.
Undifferentiated
Tbx
1
(
-
/
-
)
and
Tbx
1
(
+
/
+
)
iPSCs
showed
similar
expression
levels
of
pluripotent
markers
.
The
ability
of
the
Tbx
1
(
-
/
-
)
iPSCs
to
generate
endodermal
and
mesodermal
lineages
was
compromised
upon
spontaneous
differentiation
into
embryonic
bodies
.
Restoration
of
Tbx
1
expression
in
the
Tbx
1
(
-
/
-
)
iPSCs
to
normal
levels
using
an
inducible
lentiviral
system
rescued
these
cells
from
the
potential
of
defective
differentiation
.
Interestingly
,
overexpression
of
Tbx
1
in
the
Tbx
1
(
-
/
-
)
iPSCs
to
higher
levels
than
in
the
Tbx
1
(
+
/
+
)
iPSCs
again
led
to
a
defective
differentiation
potential
.
Additionally
,
we
observed
that
expression
of
fibroblast
growth
factor
(
FGF
)
10
and
FGF
8
was
downregulated
in
the
Tbx
1
(
-
/
-
)
iPSC-derived
cells
,
which
suggests
that
Tbx
1
regulates
the
expression
of
FGFs
.
Taken
together
,
our
results
implicated
the
Tbx
1
level
as
an
important
determinant
of
endodermal
and
mesodermal
lineage
differentiation
during
embryonic
development
.
