Epigenome dynamics during lineage specification in the mouse blastocyst
The mouse blastocyst provides a unique system for examining the specification and maintenance of lineage-restricted progenitor cells. These developmental events coincide with genome-wide changes in epigenetic modifications, including global loss of DNA methylation, raising the possibility that lineage-specification may have an uncharacterised epigenetic component.
The limited material available from blastocysts, in addition to their tissue heterogeneity, has restricted thorough investigation of lineage-specific epigenetic changes.
To address these challenges, we have previously identified cell-surface protein markers that enable prospective isolation and characterisation of the three blastocyst lineages by flow cytometry. Using this approach, we are profiling changes in epigenetic modifications in a lineage-specific manner during early mouse development.
Results could reveal how epigenetic processes impact cell fate decisions in vivo, with potentially important consequences for reproductive technologies and long-term epigenetic effects.
We have identified proteins that distinguish and visualise the three early cell lineages of the mouse embryo, shown here in blue, green and red (left panel). We now use antibodies raised against these proteins, in combination with flow cytometry (right panel), to prospectively isolate and functionally characterise each cell type directly from the embryo