Intersection of Regulatory Pathways Controlling Hemostasis and Hemochorial Placentation [human]

Tissue factor pathway inhibitor (TFPI) is a prominent regulator of blood coagulation and an intriguing constituent of trophoblast cells situated at the maternal-fetal interface. The actions of TFPI extend beyond controlling hemostasis and directly affect trophoblast cell development. TFPI facilitates the differentiation of rat and human trophoblast stem cells into the invasive trophoblast/extravillous cell lineage and promotes intrauterine trophoblast invasion and trophoblast-guided uterine spiral artery remodeling at the maternal-fetal interface. Thus, TFPI is a conserved regulator of a fundamental event determining the efficacy of the hemochorial placenta. Overall design: 1) Tfpi was knocked down in human trophoblast stem cells using lentiviral delivery of shRNA. Following selection by puromycin, cells were differentiated for eight days (Okae et al.) into extravillous trophoblast (EVT). On day eight of differentiation, cells treated with either control shRNA or Tfp1-specific shRNA were collected and RNA was isolated.