Submitted August 28, 2006
Returned for revision September 12, 2006
Accepted January 18, 2007
Pregnancy
Heat Shock Protein 1 and the Mitogen-Activated Protein
Kinase 14 Pathway Are Important for Mouse Trophoblast Stem
Cell Differentiation
Quinton Winger *,
Jillian Guttormsen ,
Heather Gavin ,
and
Frances Bhushan
* To whom correspondence should be addressed. E-mail: qwinger{at}cc.usu.edu.
Abstract
Differentiation of trophoblast cells is a critical process
for the proper establishment of the placenta and is
therefore, necessary to maintain embryonic development.
Trophoblast stem (TS) cells grown in culture can
differentiate into different trophoblast subtypes in vitro
mimicking normal trophoblast cell differentiation.
Therefore, TS cells are a valuable model system that can
be used to elucidate genetic factors that regulate
trophoblast cell differentiation. Several transcription
factors, when analyzed by targeted gene mutation in mice,
have resulted in embryonic lethality due to placental
defects and more specifically defects of the trophoblast
lineages. These studies have helped improve our knowledge
about trophoblast cell differentiation, but much is still
unknown about the specific mechanisms involved. This study
uses TS cell culture to detect proteins with differential
expression in proliferating and differentiating TS cells
in order to identify proteins with potential roles in the
differentiation process. We identified four proteins with
differential expression DDAH1, keratin 8, keratin 18 and
HSPB1 (also known as heat shock protein 25, HSP25).
Further investigation confirmed the presence of HSPB1
protein during in vitro TS cell differentiation. In
addition, we confirmed that phosphorylation of HSPB1 and
MAPKAPK2 increased in TS cells during differentiation.
Inhibition of MAPK14 (also known as p38 MAPK) resulted in
a reduction of HSPB1 phosphorylation and an increase in
cell death during TS cell differentiation. These results
suggest that HSPB1 and the MAPK14 pathway are important
during TS cell differentiation.
Key words:
Pregnancy •
Early development •
Kinases •
Placenta •
Trophoblast
