TY - JOUR
T1 - Hypoxia-inducible factors 1α and 2α regulate trophoblast differentiation
AU - Cowden Dahl, Karen D.
AU - Fryer, Benjamin H.
AU - Mack, Fiona A.
AU - Compernolle, Veerle
AU - Maltepe, Emin
AU - Adelman, David M.
AU - Carmeliet, Peter
AU - Simon, M. Celeste
PY - 2005/12
Y1 - 2005/12
N2 - Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), H/F1α and HIF2α, are essential for determining marine placental cell fates. HIF is a heterodimer composed of HIFα and HIFβ (ARNT) subunits. Placentas from Arnt-/- and Hif1α-/- Hif2α-/- embryos exhibit defective placental vascularization and aberrant cell fate adoption. HIF regulation of Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast giant cell differentiation. In the absence of Arnt or Hifα, trophoblast stem cells fail to generate these cell types and become labyrinthine trophoblasts instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, aad cell fate decisions, demonstrating that O2 tension is a critical regulator of trophoblast lineage determination. This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia.
AB - Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), H/F1α and HIF2α, are essential for determining marine placental cell fates. HIF is a heterodimer composed of HIFα and HIFβ (ARNT) subunits. Placentas from Arnt-/- and Hif1α-/- Hif2α-/- embryos exhibit defective placental vascularization and aberrant cell fate adoption. HIF regulation of Mash2 promotes spongiotrophoblast differentiation, a prerequisite for trophoblast giant cell differentiation. In the absence of Arnt or Hifα, trophoblast stem cells fail to generate these cell types and become labyrinthine trophoblasts instead. Therefore, HIF mediates placental morphogenesis, angiogenesis, aad cell fate decisions, demonstrating that O2 tension is a critical regulator of trophoblast lineage determination. This novel genetic approach provides new insights into the role of O2 tension in the development of life-threatening pregnancy-related diseases such as preeclampsia.
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U2 - 10.1128/MCB.25.23.10479-10491.2005
DO - 10.1128/MCB.25.23.10479-10491.2005
M3 - Article
C2 - 16287860
AN - SCOPUS:27944461698
SN - 0270-7306
VL - 25
SP - 10479
EP - 10491
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 23
ER -