Oliver Tam

Dissecting the regulatory network of trophoblast stem (TS) cell development

The mammalian blastocyst contains several pluripotent stemcell populations that are specified and set-aside during early embryonic development. From these populations, we can derive embryonic stem (ES) cells, which can give rise to all cell types in the adult organism, and extra-embryonic stem cells, which form structures that are critical for supporting embryonic growth. In the mouse, trophoblast stem (TS) cells are derived form the extra-embryonic stem cell population, and later give rise to the majority of the placenta. Although several genes have been identified to be important for their growth and differentiation, the molecular interactions of these genes remain largely unknown.

Building on previous studies, we will undertake genome-wide approaches to identify the core regulatory network in TS cells. Chromatin precipitation will be performed using antibodies against key TS transcriptional regulators to identify genomic regions bound by these factors. These will then be correlated with regions of active enhancer elements to identify regions of active transcription in TS cells. We hope to identify novel transcriptional regulators involved in TS cell development, and elucidate the transcriptional regulatory network that governs their maintenance and differentiation.

From this, we aim to gain greater insights into how extra-embryonic stem cells are specified, maintained and lineage-restricted in mouse and human development.