First published online July 12, 2005
Development 132, 1503e (2005)
© The Company of Biologists Limited
HIFs: regulating placental stem cell fates
During the development of placental animals, trophoblast stem (TS) cells
differentiate into the multiple specialized cells of the placenta. Now, on
p. 3393, Maltepe and
colleagues show that crosstalk between hypoxia-inducible factor (HIF) and
histone deacetylase (HDAC) determines placental stem cell fate in mice. TS
cells normally differentiate in vitro into spongiotrophoblasts and trophoblast
giant cells; however, TS cells null for Arnt, which encodes one of
the two subunits of HIF1, differentiate instead into chorionic trophoblasts
and syncytiotrophoblasts. HDAC activity is reduced in the Arnt-null
TS cells, and given that HDAC inhibition mimics ARNT deletion, the researchers
conclude that HIF-HDAC interactions regulate TS cell fate. HIFs, they suggest,
modulate the developmental plasticity of TS cells, and possibly other stem
cells, by integrating multiple epigenetic inputs, including oxygen tension and
histone acetylation, with transcriptional regulatory mechanisms.
Related articles in Development:
- Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta
- Emin Maltepe, Geoffrey W. Krampitz, Kelly M. Okazaki, Kristy Red-Horse, Winifred Mak, M. Celeste Simon, and Susan J. Fisher
Development 2005 132: 3393-3403.
[Abstract]
[Full Text]
