Transcriptional modelling of primordial germ cells.
Primordial germ cells are the founder cells of the germ line and transmit genetic and epigenetic information between the generations of an organism. Three factors, BLIMP1, AP2gamma and PRDM14 have recently been shown to be sufficient for the induction of mouse PGC-like cells in vitro and drive all the necessary gene expression changes of nascent PGCs, notably, the repression of the somatic gene expression programme, the induction of the migratory programme, repression of proliferation as well as the inititation of the unique epigenetic programme of PGCs.
We here sought to model PGC transcription including and beyond that of the initial changes during specification. First we performend principal components analysis of the gene expression profiles starting at E6.5, up until E12.5 as well as E7.5 somatic cell neightbours. We identified 5 unique gene expression patterns in this analysis. In particular we noted a major dynamic of gene expression changes upon PGC entry to the gonads around E10.5.
Additionally we modelled combinatorial genome wide binding data from several different transcriptional regulators generated in mouse ES cells, we found that the binding data, which is modelled independently of the expression data, had a statistically significant predictive power on PGC gene expression, as well as revealing novel regulatory relationships between PGC expressed factors.