miRNA regulation of the ES cell : trophoblast transition
(Laura Bailey: collaboration with Tom Burdon)
Embryonic development is a complex process that requires accurate spatial and temporal regulation of gene expression. The first obvious differentiation event to occur in the early embryo is the appearance of the trophoblast and inner cell mass (ICM) compartments. Trophoblast lineages will go on to form the embryonic portion of the placenta; while cells derived from the inner cell mass will form the embryo proper. miRNAs represent a novel form of post-transcriptional genetic that is thought to be crucial for correct embryonic development.
The differentiation of trophoblast can be modelled in the laboratory using embryonic stem (ES) cells, and we have used this system to identify miRNAs that are differentially expressed during the ES cell to trophoblast transition. We are now carrying out functional analyses on these miRNAs and to that end we have obtained a line of miRNA-deficient ES cells. We will use this in vitro model to address the following questions:
- Do ES cells require miRNAs in order to differentiate into trophoblast?
- Can we identify direct miRNA targets in ES cells?