In mammals, the placenta mediates the physiological exchange of nutrients, oxygen, hormones, metabolic by-products, and other molecules between the maternal and fetal bloodstreams. The placenta is built of several specialized cell types that are thought to originate from common stem cell precursors called trophoblast stem (TS) cells. Mouse TS cells can be cultured in vitro and, under the right conditions, self-renew indefinitely while retaining the ability to differentiate into specialized trophoblast cell types. We use mouse TS cells to model and investigate molecular mechanisms driving cell fate specification during trophoblast development.
The main aims of our research are:
We use genetic manipulations (gene knock-down/knock-in, overexpression, CRISPR/Cas9 system) to investigate the molecular events driving mouse TS cell self-renewal and differentiation. This genetic cell engineering approach is complemented by proteomic, transcriptomic and epigenetic analyses.
The murine embryo at the developmental stage E3.5 consists of the inner cells mass (ICM) and two types of trophectoderm: mural (mTE) and polar (pTE). The pTE gives rise to the extraembryonic ectoderm (ExE) and the ectoplacental cone (EPC) of the E8.0 embryo. Trophoblast stem (TS) cells can be derived from both pTE and ExE. At E8.5 chorioallantoic attachment takes place as a result of chorion and allantois coming together followed by extensive branching. The placenta at E14.5, is built of three layers: the maternal-derived decidua, the spongiotrophoblast and the labyrinth, where the actual exchange takes place between maternal and fetal bloodstrea