Placental Development

The placenta is the first organ to form following implantation of mammalian embryos. It derives from the outer layer of cells comprising the blastocyst—the trophectoderm. The rapid expansion and differentiation of TE cells gives rise to the mature placenta comprised of at least 8 different cell types. This organ enables transport of nutrients and wastes between the maternal and fetal circulations, while preventing rejection of the fetus by the maternal immune system.

Trophoblast stem cells

TSCs can be derived from  the  rodent blastocyst or early embryo and gives rise to many of the cell types comprising the mature placenta. We have been studying the ability of the Hypoxia-inducible Factor (HIF) family of transcriptional regulators to determine cell fate decisions  of TSCs. We have discovered novel  oxygen- and canonical target gene-independent roles for HIF in this process.

cytoskeleton

We surprisingly discovered that HIF aids invasive trophoblast differentiation by promoting cytoskeletal integrity in the placenta. We have also found that disruptions of this mechanism contribute to the disease process preeclampsia in humans.