REST knock-out ESCs: a role for REST in embryonic stem cells' cardiac lineage specification

During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we analyzed the effect of REST knock-out on the ability to these cells to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective down-regulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals. We propose here a new role for REST in cell fate specification besides its well-known repressive role of neuronal differentiation. REST knock-out (REST-/-) and control cells (REST+/+) were induced to differentiate by embryoid-body (EB) formation that mimicks the early gatsrulation steps of development. After 3, 6 and 9 days EBs were collected and their transcriptome was compared to control cells (d0).